Mutagenetix > Incidental Mutation

Incidental Mutation 'R7509:Hmbs'

581962

Institutional Source

Beutler Lab

Gene Symbol

Hmbs

Ensembl Gene

ENSMUSG00000032126

Gene Name

hydroxymethylbilane synthase

Synonyms

Uros1, Ups, porphobilinogen deaminase, PBGD

MMRRC Submission

045582-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7509 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

44247645-44255525 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 44248208 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Serine at position 125 (R125S)

Gene Model

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

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

SMART Domains

Protein: ENSMUSP00000076575
Gene: ENSMUSG00000032126

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

SMART Domains

Protein: ENSMUSP00000095166
Gene: ENSMUSG00000032126

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

probably benign
Transcript: ENSMUST00000215050

Predicted Effect

probably benign
Transcript: ENSMUST00000215091

Predicted Effect

probably benign
Transcript: ENSMUST00000216852

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 98.9%

Validation Efficiency

100% (75/75)

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: 76 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acsm5	A	G	7: 119,133,611 (GRCm39)	S259G	probably benign	Het
Adamts16	G	T	13: 70,935,283 (GRCm39)	N436K	probably damaging	Het
Asb3	T	A	11: 30,948,507 (GRCm39)	M61K	probably benign	Het
Catspere2	A	G	1: 177,905,078 (GRCm39)	T163A	possibly damaging	Het
Ccser2	A	G	14: 36,660,602 (GRCm39)	L517P	probably damaging	Het
Cd226	A	G	18: 89,265,195 (GRCm39)	T158A	probably benign	Het
Chd6	A	T	2: 160,855,074 (GRCm39)	I778N	probably damaging	Het
Cnga4	T	C	7: 105,056,097 (GRCm39)	V336A	probably benign	Het
Cpd	C	T	11: 76,688,702 (GRCm39)	V857I	probably benign	Het
Cpm	A	G	10: 117,495,745 (GRCm39)	Y78C	probably damaging	Het
Cst7	A	T	2: 150,419,624 (GRCm39)	T97S	probably benign	Het
Cttnbp2nl	T	C	3: 104,940,046 (GRCm39)	K8E	possibly damaging	Het
Erbb4	A	T	1: 68,289,739 (GRCm39)	D767E	possibly damaging	Het
Esyt2	T	C	12: 116,329,496 (GRCm39)	S685P	probably damaging	Het
Fam110d	A	C	4: 133,979,424 (GRCm39)	V18G	probably damaging	Het
Gcfc2	T	C	6: 81,930,256 (GRCm39)	L641P	probably damaging	Het
Gcnt4	T	A	13: 97,083,678 (GRCm39)	F325I	probably benign	Het
Glg1	T	G	8: 111,985,675 (GRCm39)	S52R	probably benign	Het
Gm10577	G	A	4: 100,877,848 (GRCm39)	L16F	unknown	Het
Gm14326	C	T	2: 177,587,493 (GRCm39)	G501D	probably benign	Het
Gm1587	G	A	14: 78,034,464 (GRCm39)	P35S	unknown	Het
Gpd1	G	A	15: 99,619,967 (GRCm39)	S255N	probably damaging	Het
Helb	T	A	10: 119,925,719 (GRCm39)	H886L	probably damaging	Het
Hgsnat	A	G	8: 26,445,754 (GRCm39)	V380A	probably damaging	Het
Hsd17b4	A	T	18: 50,297,749 (GRCm39)	Y346F	probably damaging	Het
Inpp4a	T	C	1: 37,426,911 (GRCm39)	L624P	probably damaging	Het
Irak2	AC	ACC	6: 113,667,859 (GRCm39)		probably null	Het
Itga11	C	T	9: 62,689,222 (GRCm39)	T1129I	probably benign	Het
Itih4	G	A	14: 30,617,404 (GRCm39)	V575I	probably benign	Het
Kcnn2	A	G	18: 45,816,187 (GRCm39)	T473A	probably benign	Het
Kidins220	T	C	12: 25,032,360 (GRCm39)	V31A	probably damaging	Het
Lrch1	G	A	14: 75,185,048 (GRCm39)	T18I	probably benign	Het
Ly6e	T	C	15: 74,830,135 (GRCm39)	F30L	probably damaging	Het
Med13l	A	G	5: 118,886,995 (GRCm39)	D1632G	probably damaging	Het
Mei4	T	A	9: 81,907,630 (GRCm39)	L320Q	probably damaging	Het
Mlip	T	G	9: 77,088,678 (GRCm39)	T197P	probably damaging	Het
Mon2	G	A	10: 122,868,457 (GRCm39)	A532V	probably benign	Het
Myh1	C	T	11: 67,101,287 (GRCm39)	P688S	probably benign	Het
Ncapg	G	A	5: 45,853,450 (GRCm39)	D900N	probably benign	Het
Neurl1b	C	G	17: 26,657,720 (GRCm39)	H219Q	probably benign	Het
Ntn4	A	G	10: 93,546,430 (GRCm39)	N361S	probably benign	Het
Nudt16l1	T	A	16: 4,757,082 (GRCm39)	H26Q	probably damaging	Het
Obscn	G	A	11: 58,942,455 (GRCm39)	T4348I	probably benign	Het
Or10d4b	T	A	9: 39,534,623 (GRCm39)	I66N	probably damaging	Het
Or8c20	T	A	9: 38,260,868 (GRCm39)	M157K	probably benign	Het
Pcdh7	T	A	5: 57,877,529 (GRCm39)	D361E	probably damaging	Het
Pcdhb7	C	A	18: 37,475,074 (GRCm39)	T70K	possibly damaging	Het
Pcdhga3	T	A	18: 37,808,910 (GRCm39)	Y454*	probably null	Het
Pigc	A	T	1: 161,798,545 (GRCm39)	T176S	probably benign	Het
Pola2	A	T	19: 6,011,194 (GRCm39)	S43R	probably benign	Het
Pole	A	T	5: 110,478,571 (GRCm39)		probably benign	Het
Polq	C	A	16: 36,880,705 (GRCm39)	D956E	probably benign	Het
Polq	T	A	16: 36,880,706 (GRCm39)	C957S	probably benign	Het
Ppp3cc	G	A	14: 70,504,131 (GRCm39)	T107I	probably damaging	Het
Prss39	C	A	1: 34,539,280 (GRCm39)	H173Q	possibly damaging	Het
Reep4	A	G	14: 70,785,928 (GRCm39)	D256G	probably benign	Het
Rfc3	A	G	5: 151,570,975 (GRCm39)	V107A	probably damaging	Het
Slc19a3	A	G	1: 83,003,981 (GRCm39)	L40P	probably damaging	Het
Slc29a4	C	T	5: 142,704,261 (GRCm39)	P305L	probably benign	Het
Strada	C	A	11: 106,077,920 (GRCm39)	V15F	unknown	Het
Suco	A	T	1: 161,672,903 (GRCm39)	S440T	probably damaging	Het
Svep1	A	T	4: 58,090,683 (GRCm39)	C1595S	probably benign	Het
Synpo	G	T	18: 60,736,566 (GRCm39)	T460K	probably damaging	Het
Tagap	A	T	17: 8,147,568 (GRCm39)	I93F	probably damaging	Het
Tmtc3	A	T	10: 100,301,956 (GRCm39)	F331Y	probably damaging	Het
Tnpo1	A	C	13: 99,006,751 (GRCm39)	I225M	probably benign	Het
Tollip	A	T	7: 141,445,878 (GRCm39)	M70K	probably benign	Het
Trpm7	A	T	2: 126,691,842 (GRCm39)	I171N	probably damaging	Het
Ttc41	G	T	10: 86,549,296 (GRCm39)	E163D	probably damaging	Het
Vmn2r17	A	T	5: 109,575,695 (GRCm39)	T189S	probably benign	Het
Vmn2r20	C	T	6: 123,362,382 (GRCm39)	V801I	probably benign	Het
Vmn2r82	G	A	10: 79,231,842 (GRCm39)	V614I	possibly damaging	Het
Vmn2r96	G	A	17: 18,802,995 (GRCm39)	E302K	probably benign	Het
Vwf	T	C	6: 125,619,132 (GRCm39)	F1270S		Het
Wdr3	A	T	3: 100,058,503 (GRCm39)	F367L	probably benign	Het
Zfp592	A	G	7: 80,688,088 (GRCm39)	S1005G	probably 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
R1503:Hmbs	UTSW	9	44,248,729 (GRCm39)	missense	probably benign	0.42
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
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'- ATTAAGCTGCCGTGCAACATC -3'
(R):5'- CATTTCCATGTGCACCGAAAC -3'

Sequencing Primer
(F):5'- CCTTTGTTGAGCAGCAAGC -3'
(R):5'- TTTCCATGTGCACCGAAACATCTAAG -3'

Posted On

2019-10-17