UGT1A6

protein-coding

UDP glucuronosyltransferase family 1 member A6, 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 is active on phenolic and planar compounds. Alternative splicing in the unique 5' end of this gene results in two transcript variants. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001072.4

Inheritance

—

ClinVar variants

P:48U:136B:37

Top phenotype

Gilbert syndrome

gnomAD constraint

pLI —, LoF o/e 0.67

Max pathogenic AF

—

Genomic locus

chr2:233,691,607-233,773,300

External References & Databases

Ensembl (ENSG00000167165)

Transcript & Mutation Effects

hg38 • Region Span ~81.7 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 UGT1A6 variants in ClinVar

15 Conditions Cataloged

not providedTotal: 289

not specifiedTotal: 188

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_001072.4. 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	2 clinvar	36
missense	5 clinvar	19 clinvar	131 clinvar	3 clinvar		158
nonsense	4 clinvar	3 clinvar	2 clinvar			9
start loss						0
frameshift	6 clinvar	5 clinvar	1 clinvar			12
splice donor/acceptor (+/-2bp)	2 clinvar	4 clinvar				6
Total	17	31	136	35	2	221

Highest pathogenic variant AF is 0.00048507

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001072.4	RefSeq	NP_001063.2	5	MANE Select
ENST00000305139.11	Ensembl	ENSP00000303174.6	5	MANE Select
NM_205862.3	RefSeq	NP_995584.1	5	Standard
ENST00000373424.5	Ensembl	ENSP00000362523.1	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)
nicotine degradation III
Metabolism of xenobiotics by cytochrome P450 - Homo sapiens (human)
Drug metabolism - other enzymes - Homo sapiens (human)

Biological Process

xenobiotic metabolic process
cellular glucuronidation
flavonoid glucuronidation
xenobiotic glucuronidation

Molecular Function

retinoic acid binding
UDP-glycosyltransferase activity
glucuronosyltransferase activity
protein homodimerization activity
protein heterodimerization 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: ENST00000305139
Coding exons: 5
Length: 81694
Individuals with no LoFs: 125651
Homozygous LoFs: 1
Heterozygous LoFs: 96
Defined: 125748
p: 0.000386

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0280	294	295	0.995	0.0000166	3489
Missense (PolyPhen)		146	142.85	1.022		1681
Synonymous	-0.399	120	115	1.05	0.00000676	1042
Loss of Function	1.35	13	19.4	0.669	0.00000110	238

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00043	0.00043	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0012	0.0012	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.00023	0.00023	rare
South Asian	0.0011	0.0011	notable
Other	0.00049	0.00049	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. This isoform has specificity for phenols. Isoform 3 lacks transferase activity but acts as a negative regulator of isoform 1 (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.581

Intolerance Scores

LoFtool: 0.915
RVIS EVS: -0.4
RVIS percentile EVS: 26.85

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.107

Gene Damage Prediction

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