AP5S1

protein-coding

adaptor related protein complex 5 subunit sigma 1, the group of Adaptor related protein complex 5

Gene summary

Involved in double-strand break repair via homologous recombination and endosomal transport. Located in cytosol; late endosome; and lysosome. Part of AP-type membrane coat adaptor complex. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

C20orf29

MANE transcript

NM_018347.3

Inheritance

—

ClinVar variants

U:46B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.01

Max pathogenic AF

—

Genomic locus

chr20:3,811,384-3,828,838

External References & Databases

Ensembl (ENSG00000125843)

Transcript & Mutation Effects

hg38 • Region Span ~17.5 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 AP5S1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 46

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018347.3. 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				1 clinvar		1
missense			46 clinvar	1 clinvar		47
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	46	2	0	48

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018347.3	RefSeq	NP_060817.1	2	MANE Select
ENST00000615891.2	Ensembl	ENSP00000481750.1	2	MANE Select
NM_001204446.2	RefSeq	NP_001191375.1	2	Standard
NM_001204447.2	RefSeq	NP_001191376.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

double-strand break repair via homologous recombination
protein transport
endosomal transport

Molecular Function

protein binding

Cellular Component

nucleoplasm
lysosome
lysosomal membrane
late endosome
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000246041
Coding exons: 2
Length: 4772
Individuals with no LoFs: 125721
Homozygous LoFs: 0
Heterozygous LoFs: 23
Defined: 125744
p: 0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.615	157	137	1.15	0.00000967	1257
Missense (PolyPhen)		41	36.025	1.1381		400
Synonymous	0.0427	61	61.4	0.993	0.00000404	460
Loss of Function	-0.0318	6	5.92	1.01	3.39e-7	56

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000063	0.000062	rare
Latino/Admixed American	0.00026	0.00026	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000071	0.000046	rare
European (Non-Finnish)	0.000089	0.000088	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: As part of AP-5, a probable fifth adaptor protein complex it may be involved in endosomal transport. According to PubMed:20613862, it is required for efficient homologous recombination DNA double-strand break repair. {ECO:0000269|PubMed:20613862, ECO:0000269|PubMed:22022230}.;

Intolerance Scores

RVIS EVS: 0.08
RVIS percentile EVS: 60.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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