UGT1A9

protein-coding

UDP glucuronosyltransferase family 1 member A9, 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 phenols. [provided by RefSeq, Jul 2008]

MANE transcript

NM_021027.3

Inheritance

—

ClinVar variants

P:48U:120B:42

Top phenotype

Gilbert syndrome

gnomAD constraint

pLI —, LoF o/e 0.71

Max pathogenic AF

—

Genomic locus

chr2:233,671,898-233,773,300

External References & Databases

Ensembl (ENSG00000241119)

Transcript & Mutation Effects

hg38 • Region Span ~101.4 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 UGT1A9 variants in ClinVar

15 Conditions Cataloged

not providedTotal: 320

not specifiedTotal: 274

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_021027.3. 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	34 clinvar	2 clinvar	38
missense	5 clinvar	19 clinvar	117 clinvar	5 clinvar	1 clinvar	147
nonsense	4 clinvar	3 clinvar	1 clinvar			8
start loss						0
frameshift	6 clinvar	5 clinvar				11
splice donor/acceptor (+/-2bp)	2 clinvar	4 clinvar				6
Total	17	31	120	39	3	210

Highest pathogenic variant AF is 0.00048507

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021027.3	RefSeq	NP_066307.1	5	MANE Select
ENST00000354728.5	Ensembl	ENSP00000346768.4	5	MANE Select
ENST00000978877.1	Ensembl	ENSP00000648694.1	4	Standard
ENST00001093968.1	Ensembl	ENSP00000763774.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Artemisinin and Derivatives Pathway, Pharmacokinetics
Benzodiazepine Pathway, Pharmacokinetics
Retinol metabolism - Homo sapiens (human)
Steroid hormone biosynthesis - Homo sapiens (human)
Metabolism of xenobiotics by cytochrome P450 - Homo sapiens (human)

Biological Process

xenobiotic metabolic process
regulation of lipid metabolic process
retinoic acid metabolic process
flavone metabolic process
cellular 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: ENST00000354728
Coding exons: 5
Length: 101448
Individuals with no LoFs: 125625
Homozygous LoFs: 0
Heterozygous LoFs: 123
Defined: 125748
p: 0.000489

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.937	346	300	1.15	0.0000173	3471
Missense (PolyPhen)		153	139.65	1.0956		1653
Synonymous	-2.38	149	116	1.28	0.00000724	1035
Loss of Function	1.19	14	19.7	0.711	0.00000111	238

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0023	0.0023	notable
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00046	0.00043	rare
South Asian	0.00062	0.00062	rare
Other	0.00066	0.00065	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 2 lacks transferase activity but acts as a negative regulator of isoform 1. {ECO:0000269|PubMed:19545173}.;

Recessive Scores

pRec: 0.581

Intolerance Scores

RVIS EVS: -0.69
RVIS percentile EVS: 15.27

Essentials

Essential (CRISPR): N
Indispensability pred.: N
Indispensability score: 0.0872

Gene Damage Prediction

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