AP4B1

Chr 1AR

adaptor related protein complex 4 subunit beta 1

Also known as: BETA-4, CPSQ5, SPG47

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.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.831 OMIM phenotype
Clinical SummaryAP4B1
🧬
Gene-Disease Validity (ClinGen)
AP-4 deficiency syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
📖
GeneReview available — AP4B1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.83LOEUF
pLI 0.000
Z-score 2.37
OE 0.57 (0.400.83)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.13Z-score
OE missense 0.98 (0.901.07)
398 obs / 405.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.57 (0.400.83)
00.351.4
Missense OE0.98 (0.901.07)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 20 / 35.1Missense obs/exp: 398 / 405.4Syn Z: -0.06
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongAP4B1-related cerebral palsy spastic quadriplegicLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6260th %ile
GOF
0.6052th %ile
LOF
0.2776th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

AP4B1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →