UGT1A7

protein-coding

UDP glucuronosyltransferase family 1 member A7, the group of UDP glucuronosyltransferases

Gene summary

This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The enzyme encoded by this gene has moderate glucuronidase activity with phenols. [provided by RefSeq, Jul 2008]

MANE transcript

NM_019077.3

Inheritance

—

ClinVar variants

P:48U:138B:48

Top phenotype

Gilbert syndrome

gnomAD constraint

pLI —, LoF o/e 1.01

Max pathogenic AF

—

Genomic locus

chr2:233,681,901-233,773,300

External References & Databases

Ensembl (ENSG00000244122)

Transcript & Mutation Effects

hg38 • Region Span ~91.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to UGT1A7 variants in ClinVar

15 Conditions Cataloged

not providedTotal: 317

not specifiedTotal: 234

Gilbert syndromeTotal: 93

UGT1A1-related disorderTotal: 92

Lucey-Driscoll syndromeTotal: 77

Crigler-Najjar syndrome type 1Total: 65

Crigler-Najjar syndrome, type IITotal: 58

Crigler-Najjar syndromeTotal: 40

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_019077.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	32 clinvar	1 clinvar	35
missense	5 clinvar	19 clinvar	130 clinvar	14 clinvar	1 clinvar	169
nonsense	4 clinvar	3 clinvar	4 clinvar			11
start loss						0
frameshift	6 clinvar	5 clinvar	2 clinvar			13
splice donor/acceptor (+/-2bp)	2 clinvar	4 clinvar				6
Total	17	31	138	46	2	234

Highest pathogenic variant AF is 0.00048507

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_019077.3	RefSeq	NP_061950.2	5	MANE Select
ENST00000373426.4	Ensembl	ENSP00000362525.3	5	MANE Select
ENST00000485022.1	Ensembl	ENSP00000420181.1	3	Standard
ENST00001093975.1	Ensembl	ENSP00000763781.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Retinol metabolism - Homo sapiens (human)
Steroid hormone biosynthesis - Homo sapiens (human)
Metabolism of xenobiotics by cytochrome P450 - Homo sapiens (human)
Drug metabolism - other enzymes - Homo sapiens (human)
Drug metabolism - cytochrome P450 - Homo sapiens (human)

Biological Process

excretion
coumarin metabolic process
drug metabolic process
retinoic acid metabolic process
negative regulation of catalytic activity

Molecular Function

retinoic acid binding
enzyme inhibitor activity
protein kinase C binding
UDP-glycosyltransferase activity
glucuronosyltransferase activity

Cellular Component

endoplasmic reticulum
endoplasmic reticulum membrane
integral component of membrane
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000373426
Coding exons: 5
Length: 91362
Individuals with no LoFs: 125537
Homozygous LoFs: 0
Heterozygous LoFs: 211
Defined: 125748
p: 0.000839

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.411	314	294	1.07	0.0000173	3463
Missense (PolyPhen)		142	135.35	1.0492		1605
Synonymous	-2.56	150	115	1.30	0.00000726	1049
Loss of Function	-0.0316	20	19.8	1.01	0.00000118	237

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0054	0.0054	notable
Latino/Admixed American	0.00049	0.00049	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00054	0.00054	rare
Finnish	0.00065	0.00065	rare
European (Non-Finnish)	0.00055	0.00055	rare
South Asian	0.00062	0.00062	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1. {ECO:0000269|PubMed:23360619}.;

Recessive Scores

pRec: 0.581

Intolerance Scores

LoFtool: 0.989
RVIS EVS: -0.15
RVIS percentile EVS: 42.23

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0472

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium