ICA1

protein-coding

islet cell autoantigen 1, the group of AH domain containing

Gene summary

This gene encodes a protein with an arfaptin homology domain that is found both in the cytosol and as membrane-bound form on the Golgi complex and immature secretory granules. This protein is believed to be an autoantigen in insulin-dependent diabetes mellitus and primary Sjogren's syndrome. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Feb 2013]

MANE transcript

NM_001136020.3

Inheritance

—

ClinVar variants

U:90B:4

Top phenotype

ICA1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.35

Max pathogenic AF

—

Genomic locus

chr7:8,113,184-8,262,687

External References & Databases

Ensembl (ENSG00000003147)

Transcript & Mutation Effects

hg38 • Region Span ~149.5 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 ICA1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 84

not providedTotal: 3

ICA1-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001136020.3. 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	2
missense			84 clinvar	2 clinvar		86
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	90	2	2	94

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 159 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001136020.3	RefSeq	NP_001129492.1	13	MANE Select
ENST00000402384.8	Ensembl	ENSP00000385570.3	13	MANE Select
NM_001276478.2	RefSeq	NP_001263407.1	13	Standard
NM_001350819.2	RefSeq	NP_001337748.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Type I diabetes mellitus - Homo sapiens (human)

Biological Process

neurotransmitter transport
regulation of insulin secretion

Molecular Function

molecular_function
protein binding
protein domain specific binding

Cellular Component

Golgi membrane
cytoplasm
cytosol
cell junction
secretory granule membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000402384
Coding exons: 13
Length: 149504
Individuals with no LoFs: 125731
Homozygous LoFs: 0
Heterozygous LoFs: 17
Defined: 125748
p: 0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.492	236	258	0.914	0.0000138	3177
Missense (PolyPhen)		80	114.09	0.7012		1376
Synonymous	-0.470	107	101	1.06	0.00000620	863
Loss of Function	3.39	11	31.6	0.349	0.00000163	374

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0.00014	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in neurotransmitter secretion. {ECO:0000250}.;

Recessive Scores

pRec: 0.192

Intolerance Scores

LoFtool: 0.166
RVIS EVS: -0.71
RVIS percentile EVS: 14.5

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.638

Gene Damage Prediction

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