AP5B1

Chr 11

adaptor related protein complex 5 subunit beta 1

Also known as: AP-5, PP1030

NCBI Gene: 91056 ENSG00000254470 UniProt: Q2VPB7 OMIM: 614367

The AP5B1 protein is part of the AP-5 adaptor protein complex involved in endosomal transport and is located in lysosomal membranes. Mutations cause autosomal recessive spastic paraplegia with developmental delay and seizures, typically presenting in early childhood. This gene shows extreme intolerance to loss-of-function variants, indicating that biallelic mutations are required for disease manifestation.

OMIM ResearchSummary from RefSeq, UniProt

Involved in endosomal transport. Located in lysosomal membrane. Part of AP-type membrane coat adaptor complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.24

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.24LOEUF

pLI 0.000

Z-score 0.71

OE 0.84 (0.58–1.24)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.69Z-score

OE missense 1.09 (1.01–1.17)

506 obs / 464.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.84 (0.58–1.24)

0≤0.351.4

Missense OE?1.09 (1.01–1.17)

0≤0.61.4

Synonymous OE?1.20

0≤1.21.6

LoF obs/exp: 18 / 21.6Missense obs/exp: 506 / 464.3Syn Z: -2.34

Background carrier burden — how many people carry a rare variant somewhere in AP5B1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 42

1,392 rare PASS variants

Rare truncating (LoF)

1 in 1,100

151 rare PASS variants

Rare synonymous (reference)

1 in 66

740 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for AP5B1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 52	1 in 1,200
South Asian	~43k	1 in 38	1 in 1,000
Remaining (unassigned)	~30k	1 in 32	1 in 1,400
European (Finnish)	~26k	1 in 140	1 in 2,800
Admixed American	~22k	1 in 33	1 in 1,600
African / African American	~21k	1 in 37	1 in 540
East Asian	~20k	1 in 43	1 in 2,500
Ashkenazi Jewish	~13k	1 in 110	1 in 2,200
Middle Eastern	~2,884	1 in 39	1 in 460

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 1 of 2 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 2.? see exons ↓