Mutagenetix > Incidental Mutation

Incidental Mutation 'R1503:Hmbs'

169458

Institutional Source

Beutler Lab

Gene Symbol

Hmbs

Ensembl Gene

ENSMUSG00000032126

Gene Name

hydroxymethylbilane synthase

Synonyms

Uros1, Ups, porphobilinogen deaminase, PBGD

MMRRC Submission

039553-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1503 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

44247645-44255525 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to C at 44248729 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Leucine to Tryptophan at position 215 (L215W)

Ref Sequence

ENSEMBL: ENSMUSP00000095166 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000052686] [ENSMUST00000054708] [ENSMUST00000077353] [ENSMUST00000097558] [ENSMUST00000215050] [ENSMUST00000216852] [ENSMUST00000215091]

AlphaFold

P22907

Predicted Effect

probably benign
Transcript: ENSMUST00000052686

SMART Domains

Protein: ENSMUSP00000051432
Gene: ENSMUSG00000049932

Domain	Start	End	E-Value	Type
H2A	3	123	1.64e-81	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000054708

SMART Domains

Protein: ENSMUSP00000056282
Gene: ENSMUSG00000032123

Domain	Start	End	E-Value	Type
transmembrane domain	10	32	N/A	INTRINSIC
transmembrane domain	60	82	N/A	INTRINSIC
Pfam:Glycos_transf_4	100	272	1.1e-38	PFAM
transmembrane domain	277	299	N/A	INTRINSIC
transmembrane domain	381	403	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000077353
AA Change: L232W

PolyPhen 2 Score 0.423 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000076575
Gene: ENSMUSG00000032126
AA Change: L232W

Domain	Start	End	E-Value	Type
Pfam:Porphobil_deam	21	233	1.7e-79	PFAM
Pfam:Porphobil_deamC	244	323	6.8e-24	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000097558
AA Change: L215W

PolyPhen 2 Score 0.423 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000095166
Gene: ENSMUSG00000032126
AA Change: L215W

Domain	Start	End	E-Value	Type
Pfam:Porphobil_deam	3	219	3.9e-95	PFAM
Pfam:Porphobil_deamC	227	327	4.7e-23	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000196879

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000213709

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000214012

Predicted Effect

unknown
Transcript: ENSMUST00000216658
AA Change: L48W

Predicted Effect

probably benign
Transcript: ENSMUST00000215050

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000215934

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000214967

Predicted Effect

probably benign
Transcript: ENSMUST00000216852

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000215859

Predicted Effect

probably benign
Transcript: ENSMUST00000215091

Coding Region Coverage

1x: 99.1%
3x: 98.2%
10x: 96.1%
20x: 92.0%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the hydroxymethylbilane synthase superfamily. The encoded protein is the third enzyme of the heme biosynthetic pathway and catalyzes the head to tail condensation of four porphobilinogen molecules into the linear hydroxymethylbilane. Mutations in this gene are associated with the autosomal dominant disease acute intermittent porphyria. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice heterozygous for one null allele and a functional allele with a milder mutation exhibit typical features of acute intermittent porphyria with massive urinary excretion of aminolevulinic acid after phenobarbital treatment, erythruria, ataxia, motor dysfunction, and neurologic muscle atrophy. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 79 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Arhgef6	T	C	X: 56,383,922 (GRCm39)	M5V	probably benign	Het
Atf7ip	G	T	6: 136,583,865 (GRCm39)	V1299L	probably damaging	Het
Atp12a	A	T	14: 56,610,881 (GRCm39)	N342Y	probably damaging	Het
Atp8b5	G	A	4: 43,344,430 (GRCm39)	G439D	probably damaging	Het
Bpifb2	G	A	2: 153,731,430 (GRCm39)	D269N	possibly damaging	Het
Btd	T	G	14: 31,389,612 (GRCm39)	C444W	probably damaging	Het
Cacna1a	A	G	8: 85,328,575 (GRCm39)	D1624G	probably benign	Het
Carmil3	A	C	14: 55,735,737 (GRCm39)	N563T	probably damaging	Het
Cars1	T	C	7: 143,122,726 (GRCm39)	R538G	probably benign	Het
Catsperd	A	G	17: 56,961,525 (GRCm39)	K416E	possibly damaging	Het
Cc2d2a	A	T	5: 43,852,581 (GRCm39)	Y386F	probably damaging	Het
Ccpg1	A	G	9: 72,906,760 (GRCm39)	N66S	probably benign	Het
Cd48	T	A	1: 171,523,415 (GRCm39)	L86H	probably damaging	Het
Cdan1	A	T	2: 120,560,056 (GRCm39)	H369Q	probably damaging	Het
Chil4	T	C	3: 106,113,350 (GRCm39)	D189G	probably benign	Het
Cit	T	A	5: 116,011,959 (GRCm39)	Y189N	possibly damaging	Het
Cntn3	G	A	6: 102,441,526 (GRCm39)	Q7*	probably null	Het
Csn1s2a	A	T	5: 87,923,658 (GRCm39)	I5F	possibly damaging	Het
Ctnnd1	C	T	2: 84,435,523 (GRCm39)		probably null	Het
Dmxl2	A	T	9: 54,354,272 (GRCm39)	Y391*	probably null	Het
Dnah12	T	C	14: 26,495,649 (GRCm39)	S1426P	probably damaging	Het
Dnhd1	T	G	7: 105,342,867 (GRCm39)	S1404A	possibly damaging	Het
Drosha	T	A	15: 12,848,159 (GRCm39)	C484S	probably benign	Het
Dsg4	A	T	18: 20,582,736 (GRCm39)	I125F	probably damaging	Het
Egfr	T	A	11: 16,819,301 (GRCm39)	M277K	possibly damaging	Het
Eml5	G	T	12: 98,797,433 (GRCm39)	L1059I	probably damaging	Het
Erbb4	G	T	1: 68,385,705 (GRCm39)	H295N	probably benign	Het
Etl4	T	G	2: 20,748,685 (GRCm39)	V139G	possibly damaging	Het
Fhip1a	T	A	3: 85,579,784 (GRCm39)	Y807F	possibly damaging	Het
Frem3	A	T	8: 81,413,647 (GRCm39)	E1969D	probably damaging	Het
Gdf3	T	A	6: 122,583,296 (GRCm39)	D357V	probably damaging	Het
Gimap8	T	A	6: 48,624,463 (GRCm39)		probably null	Het
Gml2	C	A	15: 74,693,201 (GRCm39)	S68*	probably null	Het
Gphn	A	G	12: 78,551,403 (GRCm39)	I248V	possibly damaging	Het
Greb1	A	T	12: 16,774,820 (GRCm39)	Y192*	probably null	Het
Iglon5	T	A	7: 43,128,449 (GRCm39)	T123S	probably benign	Het
Ints2	C	T	11: 86,117,607 (GRCm39)	R705H	probably damaging	Het
Ints8	A	T	4: 11,245,842 (GRCm39)	L212Q	probably damaging	Het
Itgad	A	G	7: 127,797,293 (GRCm39)	Y846C	probably benign	Het
Kcnj1	A	G	9: 32,307,788 (GRCm39)	T51A	probably damaging	Het
Kif9	A	T	9: 110,339,506 (GRCm39)	K449N	possibly damaging	Het
Kifbp	A	G	10: 62,395,187 (GRCm39)	V485A	probably damaging	Het
Klk1b11	G	A	7: 43,428,333 (GRCm39)	W241*	probably null	Het
Krt32	T	C	11: 99,974,936 (GRCm39)		probably null	Het
Loxl1	A	G	9: 58,200,923 (GRCm39)	F513S	probably damaging	Het
Mapk8ip3	A	T	17: 25,123,897 (GRCm39)	S571T	probably damaging	Het
Mcam	C	T	9: 44,052,588 (GRCm39)	R606C	probably damaging	Het
Mtss1	T	C	15: 58,823,521 (GRCm39)	N282S	probably damaging	Het
Myh13	T	A	11: 67,244,500 (GRCm39)	D1012E	probably benign	Het
Myo16	A	G	8: 10,552,817 (GRCm39)	T952A	probably benign	Het
Neb	T	C	2: 52,188,632 (GRCm39)	D874G	probably damaging	Het
Nek11	A	G	9: 105,040,403 (GRCm39)	Y553H	probably damaging	Het
Nr2c2	T	A	6: 92,082,312 (GRCm39)	V9D	probably benign	Het
Nxf1	T	A	19: 8,739,800 (GRCm39)	F51L	probably benign	Het
Or1e1f	T	G	11: 73,855,394 (GRCm39)		probably null	Het
Or1j15	A	T	2: 36,458,885 (GRCm39)	I92F	probably damaging	Het
Or2aj5	A	G	16: 19,425,062 (GRCm39)	S119P	probably benign	Het
Or4c35	T	C	2: 89,808,872 (GRCm39)	V250A	probably damaging	Het
Or5bw2	A	G	7: 6,573,470 (GRCm39)	N160S	probably damaging	Het
Or6s1	A	G	14: 51,308,191 (GRCm39)	S220P	probably damaging	Het
Or6z6	T	C	7: 6,491,178 (GRCm39)	I232V	probably damaging	Het
Pcdhb8	A	T	18: 37,489,572 (GRCm39)	N76Y	probably damaging	Het
Pdzrn4	T	A	15: 92,297,685 (GRCm39)	F217I	probably damaging	Het
Ppp1r16a	T	A	15: 76,578,599 (GRCm39)	H434Q	probably benign	Het
Prpf19	T	A	19: 10,878,386 (GRCm39)	F291I	possibly damaging	Het
R3hdm2	G	T	10: 127,307,695 (GRCm39)	E319*	probably null	Het
Sel1l3	A	G	5: 53,295,271 (GRCm39)	Y777H	probably damaging	Het
Serpinb5	G	A	1: 106,798,019 (GRCm39)	A3T	possibly damaging	Het
Skp2	C	A	15: 9,127,998 (GRCm39)	V88F	probably damaging	Het
Slc25a16	T	C	10: 62,764,155 (GRCm39)	Y71H	probably damaging	Het
Slc6a6	T	A	6: 91,717,973 (GRCm39)	I304N	probably damaging	Het
Sned1	G	A	1: 93,209,376 (GRCm39)	V830M	possibly damaging	Het
Sox17	C	A	1: 4,562,151 (GRCm39)	G222C	probably damaging	Het
Trmu	T	A	15: 85,779,220 (GRCm39)	V289E	possibly damaging	Het
Vdac2	A	G	14: 21,887,945 (GRCm39)	E96G	probably damaging	Het
Wdhd1	A	T	14: 47,484,857 (GRCm39)	D885E	probably benign	Het
Zfp646	A	G	7: 127,479,308 (GRCm39)	N495S	probably damaging	Het
Zfp663	T	C	2: 165,194,573 (GRCm39)	T549A	probably damaging	Het
Zfp935	G	A	13: 62,602,951 (GRCm39)	A83V	possibly damaging	Het

Other mutations in Hmbs

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01526:Hmbs	APN	9	44,250,845 (GRCm39)	missense	possibly damaging	0.91
IGL02312:Hmbs	APN	9	44,252,510 (GRCm39)	critical splice donor site	probably null
R0386:Hmbs	UTSW	9	44,248,305 (GRCm39)	missense	probably benign	0.06
R0411:Hmbs	UTSW	9	44,252,949 (GRCm39)	nonsense	probably null
R0656:Hmbs	UTSW	9	44,248,657 (GRCm39)	missense	probably benign	0.31
R1560:Hmbs	UTSW	9	44,248,657 (GRCm39)	missense	possibly damaging	0.71
R1953:Hmbs	UTSW	9	44,248,741 (GRCm39)	missense	probably damaging	1.00
R2127:Hmbs	UTSW	9	44,252,004 (GRCm39)	missense	probably benign	0.09
R4637:Hmbs	UTSW	9	44,250,834 (GRCm39)	missense	probably damaging	1.00
R5549:Hmbs	UTSW	9	44,250,774 (GRCm39)	critical splice donor site	probably null
R6611:Hmbs	UTSW	9	44,252,988 (GRCm39)	missense	probably damaging	0.98
R7509:Hmbs	UTSW	9	44,248,208 (GRCm39)	missense
R7702:Hmbs	UTSW	9	44,248,147 (GRCm39)	splice site	probably null
R8383:Hmbs	UTSW	9	44,249,240 (GRCm39)	missense	probably damaging	1.00
R8506:Hmbs	UTSW	9	44,252,921 (GRCm39)	critical splice donor site	probably null
R9069:Hmbs	UTSW	9	44,248,102 (GRCm39)	missense	possibly damaging	0.79
R9149:Hmbs	UTSW	9	44,252,983 (GRCm39)	nonsense	probably null
R9780:Hmbs	UTSW	9	44,247,985 (GRCm39)	missense	probably damaging	1.00
X0024:Hmbs	UTSW	9	44,249,265 (GRCm39)	missense	possibly damaging	0.89

Predicted Primers

PCR Primer
(F):5'- ATGGAAATGACAGTCCCTCCCCTC -3'
(R):5'- TGGTTCATAACCTTTGGCACCTGC -3'

Sequencing Primer
(F):5'- TTTTGACCACAGACCTCAAGGG -3'
(R):5'- GGCACCTGCTATCCATCAAATAAG -3'

Posted On

2014-04-13