Mutagenetix > Incidental Mutation

Incidental Mutation 'R4060:Cfh'

315802

Institutional Source

Beutler Lab

Gene Symbol

Cfh

Ensembl Gene

ENSMUSG00000026365

Gene Name

complement component factor h

Synonyms

Sas-1, Mud-1, Sas1

MMRRC Submission

041618-MU

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.105) question?

Stock #

R4060 (G1)

Quality Score

163

Status

Not validated

Chromosome

Chromosomal Location

140013593-140111149 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 140047664 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Methionine at position 488 (I488M)

Ref Sequence

ENSEMBL: ENSMUSP00000066677 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000066859] [ENSMUST00000111976] [ENSMUST00000111977] [ENSMUST00000123238] [ENSMUST00000192880]

AlphaFold

P06909

PDB Structure

Structure of domains 6 and 7 of the mouse complement regulator Factor H [X-RAY DIFFRACTION]

Predicted Effect

possibly damaging
Transcript: ENSMUST00000066859
AA Change: I488M

PolyPhen 2 Score 0.907 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000066677
Gene: ENSMUSG00000026365
AA Change: I488M

Domain	Start	End	E-Value	Type
CCP	21	80	7.75e-8	SMART
CCP	85	141	2.17e-11	SMART
CCP	146	205	7.5e-15	SMART
CCP	210	262	6.29e-8	SMART
CCP	267	320	2.04e-7	SMART
CCP	325	385	6.35e-4	SMART
CCP	389	442	1.15e-10	SMART
CCP	448	505	3.62e-8	SMART
CCP	509	564	6.45e-5	SMART
CCP	569	622	5.56e-9	SMART
CCP	629	683	3.45e-14	SMART
CCP	690	743	1.82e-13	SMART
CCP	752	802	6.59e-1	SMART
CCP	808	861	1.04e-8	SMART
CCP	867	931	4.66e-11	SMART
CCP	936	989	3.9e-13	SMART
CCP	994	1048	1.4e-14	SMART
CCP	1053	1107	2.09e-13	SMART
CCP	1114	1168	8.04e-15	SMART
CCP	1172	1233	5.57e0	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000111976
AA Change: I506M

PolyPhen 2 Score 0.046 (Sensitivity: 0.94; Specificity: 0.83)

SMART Domains

Protein: ENSMUSP00000107607
Gene: ENSMUSG00000026365
AA Change: I506M

Domain	Start	End	E-Value	Type
CCP	39	98	7.75e-8	SMART
CCP	103	159	2.17e-11	SMART
CCP	164	223	7.5e-15	SMART
CCP	228	280	6.29e-8	SMART
CCP	285	338	2.04e-7	SMART
CCP	343	403	6.35e-4	SMART
CCP	407	460	1.15e-10	SMART
CCP	466	523	3.62e-8	SMART
CCP	527	582	6.45e-5	SMART
CCP	587	640	5.56e-9	SMART
CCP	647	701	3.45e-14	SMART
CCP	708	761	1.82e-13	SMART
CCP	770	820	6.59e-1	SMART
CCP	826	879	1.04e-8	SMART
CCP	885	949	4.66e-11	SMART
CCP	954	1007	3.9e-13	SMART
CCP	1012	1066	1.4e-14	SMART
CCP	1071	1125	2.09e-13	SMART
CCP	1132	1186	8.04e-15	SMART
CCP	1190	1251	5.57e0	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000111977
AA Change: I506M

PolyPhen 2 Score 0.025 (Sensitivity: 0.95; Specificity: 0.81)

SMART Domains

Protein: ENSMUSP00000107608
Gene: ENSMUSG00000026365
AA Change: I506M

Domain	Start	End	E-Value	Type
CCP	21	80	7.75e-8	SMART
CCP	85	141	2.17e-11	SMART
CCP	146	205	7.5e-15	SMART
CCP	210	262	6.29e-8	SMART
CCP	267	320	2.04e-7	SMART
CCP	325	385	6.35e-4	SMART
CCP	389	442	1.15e-10	SMART
CCP	448	505	3.62e-8	SMART
CCP	509	564	6.45e-5	SMART
CCP	572	626	3.45e-14	SMART
CCP	633	686	1.82e-13	SMART
CCP	695	745	6.59e-1	SMART
CCP	751	804	1.04e-8	SMART
CCP	810	874	4.66e-11	SMART
CCP	879	932	3.9e-13	SMART
CCP	937	991	1.4e-14	SMART
CCP	996	1050	2.09e-13	SMART
CCP	1057	1111	8.04e-15	SMART
CCP	1115	1176	5.57e0	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000123238
AA Change: I488M

PolyPhen 2 Score 0.106 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000115166
Gene: ENSMUSG00000026365
AA Change: I488M

Domain	Start	End	E-Value	Type
signal peptide	1	18	N/A	INTRINSIC
CCP	21	80	7.75e-8	SMART
CCP	85	141	2.17e-11	SMART
CCP	146	205	7.5e-15	SMART
CCP	210	262	6.29e-8	SMART
CCP	267	320	2.04e-7	SMART
CCP	325	385	6.35e-4	SMART
CCP	389	442	1.15e-10	SMART
CCP	448	505	3.62e-8	SMART
CCP	509	564	6.45e-5	SMART
CCP	569	622	5.56e-9	SMART
CCP	629	683	3.45e-14	SMART
CCP	690	743	1.82e-13	SMART
CCP	752	802	6.59e-1	SMART
CCP	808	861	1.04e-8	SMART
CCP	867	931	4.66e-11	SMART
CCP	936	989	3.9e-13	SMART
CCP	994	1048	1.4e-14	SMART
CCP	1053	1107	2.09e-13	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000192880

SMART Domains

Protein: ENSMUSP00000141209
Gene: ENSMUSG00000026365

Domain	Start	End	E-Value	Type
signal peptide	1	36	N/A	INTRINSIC
CCP	39	98	3.9e-10	SMART
CCP	103	159	1e-13	SMART
CCP	164	223	3.7e-17	SMART
CCP	228	280	3.1e-10	SMART
CCP	285	338	9.9e-10	SMART
CCP	343	403	3.2e-6	SMART
CCP	407	460	5.6e-13	SMART
CCP	467	521	6.7e-17	SMART
CCP	526	580	1e-15	SMART
CCP	587	641	3.8e-17	SMART
CCP	645	706	2.7e-2	SMART

Predicted Effect

unknown
Transcript: ENSMUST00000192919
AA Change: I219M

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.4%
20x: 95.7%

Validation Efficiency

95% (41/43)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is a member of the Regulator of Complement Activation (RCA) gene cluster and encodes a protein with twenty short consensus repeat (SCR) domains. This protein is secreted into the bloodstream and has an essential role in the regulation of complement activation, restricting this innate defense mechanism to microbial infections. Mutations in this gene have been associated with hemolytic-uremic syndrome (HUS) and chronic hypocomplementemic nephropathy. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Oct 2011]
PHENOTYPE: Homozygous mutation of this gene results in markedly reduced serum C3, abnormal renal histology, spontaneous membranoproliferative glomerulonephritis (MPGN), hematuria, proteinuria, and increased mortality at 8 months of age. [provided by MGI curators]

Allele List at MGI

All alleles(2) : Targeted, knock-out(1) Targeted, other(1)

Other mutations in this stock

Total: 38 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700019A02Rik	A	T	1: 53,197,928 (GRCm39)	L140Q	probably damaging	Het
Abca8b	A	T	11: 109,848,027 (GRCm39)	M756K	probably benign	Het
Cd44	T	C	2: 102,731,687 (GRCm39)	D2G	probably damaging	Het
Cdan1	T	C	2: 120,556,224 (GRCm39)	I681V	probably benign	Het
Cdc5l	C	T	17: 45,721,816 (GRCm39)	A485T	probably benign	Het
Cntn2	T	A	1: 132,453,634 (GRCm39)	L346F	probably damaging	Het
Creb3l2	T	C	6: 37,311,484 (GRCm39)	H435R	probably benign	Het
Dmbt1	A	G	7: 130,675,932 (GRCm39)		probably benign	Het
Fam162a	C	T	16: 35,864,451 (GRCm39)	R38K	probably benign	Het
Fat1	A	T	8: 45,478,518 (GRCm39)	E2521D	probably benign	Het
Foxo1	A	G	3: 52,252,583 (GRCm39)	R249G	probably damaging	Het
Grm6	A	G	11: 50,744,051 (GRCm39)	E174G	probably damaging	Het
Gtpbp2	G	A	17: 46,478,253 (GRCm39)	R467H	probably damaging	Het
Hypk	A	G	2: 121,284,160 (GRCm39)		probably benign	Het
Ifih1	T	C	2: 62,429,143 (GRCm39)	T932A	possibly damaging	Het
Igfbp1	C	A	11: 7,148,091 (GRCm39)	P45T	probably damaging	Het
Ik	A	G	18: 36,881,943 (GRCm39)	K142E	probably damaging	Het
Ltbp3	T	C	19: 5,792,348 (GRCm39)	L27P	probably benign	Het
Mast3	A	G	8: 71,233,838 (GRCm39)	V969A	probably damaging	Het
Mrps24	G	A	11: 5,654,676 (GRCm39)	R93*	probably null	Het
Or13a20	T	C	7: 140,232,033 (GRCm39)	I47T	probably damaging	Het
Or1j14	A	G	2: 36,417,426 (GRCm39)	M1V	probably null	Het
Or7g19	T	C	9: 18,856,346 (GRCm39)	V134A	probably benign	Het
Otop2	G	A	11: 115,220,201 (GRCm39)	G347D	probably damaging	Het
Pcdhb20	A	G	18: 37,639,217 (GRCm39)	E581G	probably damaging	Het
Rnf146	T	C	10: 29,223,363 (GRCm39)	I174M	probably damaging	Het
Serpinb9g	G	A	13: 33,679,089 (GRCm39)	V320I	probably benign	Het
Sh3pxd2b	G	T	11: 32,372,263 (GRCm39)	A477S	probably benign	Het
Slc23a3	T	G	1: 75,109,964 (GRCm39)		probably benign	Het
Ssrp1	T	G	2: 84,871,978 (GRCm39)	Y401D	probably damaging	Het
Tas2r109	A	T	6: 132,957,148 (GRCm39)	W261R	probably damaging	Het
Tas2r144	T	C	6: 42,192,563 (GRCm39)	V101A	possibly damaging	Het
Tead1	T	A	7: 112,475,269 (GRCm39)		probably null	Het
Tiam2	A	G	17: 3,479,255 (GRCm39)	S663G	probably benign	Het
Trbv20	T	G	6: 41,165,195 (GRCm39)		probably benign	Het
Tspan9	T	C	6: 128,011,135 (GRCm39)	I19M	probably benign	Het
Ttbk2	T	A	2: 120,579,465 (GRCm39)	E552D	probably benign	Het
Zfp292	A	G	4: 34,810,863 (GRCm39)	V727A	probably damaging	Het

Other mutations in Cfh

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00969:Cfh	APN	1	140,016,420 (GRCm39)	missense	probably damaging	1.00
IGL01124:Cfh	APN	1	140,110,999 (GRCm39)	missense	probably benign	0.01
IGL01389:Cfh	APN	1	140,082,377 (GRCm39)	missense	probably benign	0.44
IGL01455:Cfh	APN	1	140,033,277 (GRCm39)	missense	possibly damaging	0.51
IGL01877:Cfh	APN	1	140,028,567 (GRCm39)	missense	probably damaging	1.00
IGL02836:Cfh	APN	1	140,030,137 (GRCm39)	missense	probably damaging	1.00
IGL02937:Cfh	APN	1	140,033,180 (GRCm39)	missense	probably benign	0.19
IGL03039:Cfh	APN	1	140,063,999 (GRCm39)	missense	possibly damaging	0.86
IGL03069:Cfh	APN	1	140,026,793 (GRCm39)	intron	probably benign
IGL03192:Cfh	APN	1	140,026,759 (GRCm39)	missense	possibly damaging	0.71
IGL03201:Cfh	APN	1	140,030,557 (GRCm39)	missense	probably damaging	1.00
3-1:Cfh	UTSW	1	140,090,863 (GRCm39)	missense	probably damaging	1.00
PIT4449001:Cfh	UTSW	1	140,040,303 (GRCm39)	missense	probably damaging	1.00
R0257:Cfh	UTSW	1	140,071,773 (GRCm39)	missense	probably benign	0.01
R0294:Cfh	UTSW	1	140,110,999 (GRCm39)	missense	probably benign	0.01
R0571:Cfh	UTSW	1	140,030,071 (GRCm39)	splice site	probably null
R0576:Cfh	UTSW	1	140,064,553 (GRCm39)	missense	probably damaging	0.99
R0586:Cfh	UTSW	1	140,110,920 (GRCm39)	missense	probably damaging	0.98
R0605:Cfh	UTSW	1	140,030,096 (GRCm39)	missense	probably damaging	1.00
R0617:Cfh	UTSW	1	140,028,621 (GRCm39)	missense	probably benign	0.01
R0725:Cfh	UTSW	1	140,085,081 (GRCm39)	splice site	probably benign
R0853:Cfh	UTSW	1	140,033,228 (GRCm39)	missense	probably damaging	1.00
R1430:Cfh	UTSW	1	140,030,436 (GRCm39)	splice site	probably benign
R1500:Cfh	UTSW	1	140,028,614 (GRCm39)	missense	probably damaging	1.00
R1533:Cfh	UTSW	1	140,028,716 (GRCm39)	missense	possibly damaging	0.86
R1667:Cfh	UTSW	1	140,033,261 (GRCm39)	missense	probably benign	0.01
R1695:Cfh	UTSW	1	140,030,575 (GRCm39)	missense	probably damaging	0.98
R1728:Cfh	UTSW	1	140,075,435 (GRCm39)	missense	possibly damaging	0.55
R1729:Cfh	UTSW	1	140,064,526 (GRCm39)	missense	probably benign	0.02
R1729:Cfh	UTSW	1	140,075,435 (GRCm39)	missense	possibly damaging	0.55
R1730:Cfh	UTSW	1	140,075,435 (GRCm39)	missense	possibly damaging	0.55
R1739:Cfh	UTSW	1	140,075,435 (GRCm39)	missense	possibly damaging	0.55
R1739:Cfh	UTSW	1	140,064,526 (GRCm39)	missense	probably benign	0.02
R1756:Cfh	UTSW	1	140,028,615 (GRCm39)	missense	probably damaging	1.00
R1762:Cfh	UTSW	1	140,075,435 (GRCm39)	missense	possibly damaging	0.55
R1762:Cfh	UTSW	1	140,064,526 (GRCm39)	missense	probably benign	0.02
R1783:Cfh	UTSW	1	140,075,435 (GRCm39)	missense	possibly damaging	0.55
R1784:Cfh	UTSW	1	140,075,435 (GRCm39)	missense	possibly damaging	0.55
R1785:Cfh	UTSW	1	140,075,435 (GRCm39)	missense	possibly damaging	0.55
R1785:Cfh	UTSW	1	140,064,526 (GRCm39)	missense	probably benign	0.02
R1912:Cfh	UTSW	1	140,063,879 (GRCm39)	splice site	probably null
R2273:Cfh	UTSW	1	140,030,563 (GRCm39)	missense	probably damaging	1.00
R2288:Cfh	UTSW	1	140,026,639 (GRCm39)	missense	possibly damaging	0.70
R3725:Cfh	UTSW	1	140,014,234 (GRCm39)	missense	probably damaging	0.99
R3731:Cfh	UTSW	1	140,047,708 (GRCm39)	missense	possibly damaging	0.71
R4192:Cfh	UTSW	1	140,030,454 (GRCm39)	missense	possibly damaging	0.50
R4226:Cfh	UTSW	1	140,036,664 (GRCm39)	missense	probably damaging	1.00
R4425:Cfh	UTSW	1	140,028,613 (GRCm39)	nonsense	probably null
R4431:Cfh	UTSW	1	140,064,004 (GRCm39)	missense	probably damaging	1.00
R4712:Cfh	UTSW	1	140,036,274 (GRCm39)	missense	probably damaging	1.00
R4755:Cfh	UTSW	1	140,016,546 (GRCm39)	missense	probably damaging	1.00
R4792:Cfh	UTSW	1	140,028,561 (GRCm39)	nonsense	probably null
R4831:Cfh	UTSW	1	140,014,125 (GRCm39)	missense	probably benign
R5052:Cfh	UTSW	1	140,071,782 (GRCm39)	missense	probably damaging	0.96
R5181:Cfh	UTSW	1	140,075,384 (GRCm39)	splice site	probably benign
R5205:Cfh	UTSW	1	140,071,708 (GRCm39)	missense	probably damaging	1.00
R5285:Cfh	UTSW	1	140,028,636 (GRCm39)	missense	probably benign	0.21
R5366:Cfh	UTSW	1	140,063,973 (GRCm39)	missense	probably damaging	1.00
R5776:Cfh	UTSW	1	140,071,761 (GRCm39)	missense	possibly damaging	0.83
R5914:Cfh	UTSW	1	140,063,967 (GRCm39)	missense	probably benign	0.39
R5948:Cfh	UTSW	1	140,036,546 (GRCm39)	missense	probably damaging	0.96
R5979:Cfh	UTSW	1	140,046,409 (GRCm39)	missense	possibly damaging	0.66
R6034:Cfh	UTSW	1	140,090,869 (GRCm39)	missense	probably damaging	0.98
R6034:Cfh	UTSW	1	140,090,869 (GRCm39)	missense	probably damaging	0.98
R6059:Cfh	UTSW	1	140,046,428 (GRCm39)	missense	possibly damaging	0.92
R6198:Cfh	UTSW	1	140,033,178 (GRCm39)	missense	probably damaging	1.00
R6306:Cfh	UTSW	1	140,030,155 (GRCm39)	missense	probably damaging	1.00
R6523:Cfh	UTSW	1	140,029,445 (GRCm39)	missense	possibly damaging	0.82
R6610:Cfh	UTSW	1	140,029,486 (GRCm39)	nonsense	probably null
R6652:Cfh	UTSW	1	140,071,806 (GRCm39)	missense	probably benign	0.39
R6852:Cfh	UTSW	1	140,075,487 (GRCm39)	missense	probably damaging	1.00
R6861:Cfh	UTSW	1	140,028,621 (GRCm39)	missense	probably benign	0.07
R6862:Cfh	UTSW	1	140,030,100 (GRCm39)	missense	probably damaging	1.00
R7065:Cfh	UTSW	1	140,014,140 (GRCm39)	missense	probably damaging	0.99
R7191:Cfh	UTSW	1	140,040,305 (GRCm39)	missense	probably benign	0.04
R7197:Cfh	UTSW	1	140,016,505 (GRCm39)	nonsense	probably null
R7355:Cfh	UTSW	1	140,064,553 (GRCm39)	missense	probably damaging	1.00
R7367:Cfh	UTSW	1	140,014,259 (GRCm39)	missense	probably damaging	0.97
R7419:Cfh	UTSW	1	140,033,204 (GRCm39)	missense	probably damaging	0.99
R7579:Cfh	UTSW	1	140,036,328 (GRCm39)	missense	possibly damaging	0.53
R7586:Cfh	UTSW	1	140,075,459 (GRCm39)	missense	probably damaging	0.99
R7985:Cfh	UTSW	1	140,036,564 (GRCm39)	missense	probably damaging	1.00
R8119:Cfh	UTSW	1	140,047,753 (GRCm39)	missense	possibly damaging	0.95
R8277:Cfh	UTSW	1	140,029,347 (GRCm39)	missense	probably damaging	1.00
R8742:Cfh	UTSW	1	140,029,390 (GRCm39)	missense	probably damaging	0.98
R8742:Cfh	UTSW	1	140,064,469 (GRCm39)	missense	probably damaging	0.97
R8743:Cfh	UTSW	1	140,046,323 (GRCm39)	critical splice donor site	probably null
R8874:Cfh	UTSW	1	140,014,159 (GRCm39)	missense	probably damaging	1.00
R8909:Cfh	UTSW	1	140,014,086 (GRCm39)	missense	possibly damaging	0.47
R8949:Cfh	UTSW	1	140,026,705 (GRCm39)	missense	probably damaging	0.98
R9126:Cfh	UTSW	1	140,014,111 (GRCm39)	missense	probably damaging	0.98
R9309:Cfh	UTSW	1	140,082,249 (GRCm39)	missense	probably damaging	0.99
R9441:Cfh	UTSW	1	140,030,149 (GRCm39)	missense	probably benign	0.08
R9502:Cfh	UTSW	1	140,040,320 (GRCm39)	missense	possibly damaging	0.85
R9544:Cfh	UTSW	1	140,036,266 (GRCm39)	missense	probably benign	0.14
R9559:Cfh	UTSW	1	140,030,275 (GRCm39)	missense	probably benign	0.32
R9616:Cfh	UTSW	1	140,030,254 (GRCm39)	missense	probably damaging	0.99
R9617:Cfh	UTSW	1	140,090,718 (GRCm39)	missense	possibly damaging	0.53
R9733:Cfh	UTSW	1	140,016,533 (GRCm39)	missense	probably damaging	1.00
R9748:Cfh	UTSW	1	140,090,687 (GRCm39)	critical splice donor site	probably null
R9788:Cfh	UTSW	1	140,036,499 (GRCm39)	missense	probably benign	0.01
T0975:Cfh	UTSW	1	140,082,336 (GRCm39)	missense	probably benign	0.05
Z1088:Cfh	UTSW	1	140,075,456 (GRCm39)	missense	possibly damaging	0.77
Z1088:Cfh	UTSW	1	140,036,642 (GRCm39)	missense	probably benign	0.04
Z1177:Cfh	UTSW	1	140,071,797 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- AGTTGCAGCTCTTCAAAGACTTC -3'
(R):5'- AGCTGTGCATACCCTCATTC -3'

Sequencing Primer
(F):5'- AGCTCTTCAAAGACTTCTTCACTAG -3'
(R):5'- AGCTGTGCATACCCTCATTCTTTTC -3'

Posted On

2015-05-15