AP4B1

Chr 1

adaptor related protein complex 4 subunit beta 1

Also known as: BETA-4, CPSQ5, SPG47

NCBI Gene: 10717 ENSG00000134262 UniProt: Q9Y6B7

The protein encoded by this gene is a subunit of the heterotetrameric adapter-like complex 4 that targets proteins from the trans-Golgi network to the endosomal-lysosomal system. Mutations cause spastic paraplegia 47 and cerebral palsy spastic quadriplegic type 5 through autosomal recessive inheritance. The pathogenic mechanism involves disrupted intracellular protein trafficking between the Golgi apparatus and lysosomal compartments.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a subunit of a heterotetrameric adapter-like complex 4 that is involved in targeting proteins from the trans-Golgi network to the endosomal-lysosomal system. Mutations in this gene are associated with cerebral palsy spastic quadriplegic type 5 (CPSQ5) disorder. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSpastic paraplegia 47, autosomal recessive

Clinical highlights

Gene–disease validity (ClinGen · GenCC)

Definitive · AP-4 deficiency syndrome · AR · ClinGen 2021
Strong · hereditary spastic paraplegia 47 · AR · Labcorp Genetics (formerly Invitae)
Supportive · AP4-related intellectual disability and spastic paraplegia · AR · Orphanet

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.83

LOEUF

LOF

Mechanism· G2P

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GeneReview available — AP4B1

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.83LOEUF

pLI 0.000

Z-score 2.37

OE 0.57 (0.40–0.83)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.13Z-score

OE missense 0.98 (0.90–1.07)

398 obs / 405.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.57 (0.40–0.83)

0≤0.351.4

Missense OE?0.98 (0.90–1.07)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 20 / 35.1Missense obs/exp: 398 / 405.4Syn Z: -0.06

Background carrier burden — how many people carry a rare variant somewhere in AP4B1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 71

977 rare PASS variants

Rare truncating (LoF)

1 in 980

131 rare PASS variants

Rare synonymous (reference)

1 in 140

359 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for AP4B1. 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 100	1 in 1,200
South Asian	~43k	1 in 42	1 in 610
Remaining (unassigned)	~30k	1 in 57	1 in 920
European (Finnish)	~27k	1 in 200	≈ 1 in 13,000
Admixed American	~22k	1 in 65	1 in 700
African / African American	~21k	1 in 80	1 in 960
East Asian	~20k	1 in 48	1 in 920
Ashkenazi Jewish	~13k	1 in 260	1 in 500
Middle Eastern	~2,884	1 in 54	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.