BCAP31

Chr X

B cell receptor associated protein 31

Also known as: 6C6-AG, BAP31, CDM, DDCH, DELXQ28, DXS1357E, MICRODELXq28

NCBI Gene: 10134 ENSG00000185825 UniProt: P51572

BCAP31 encodes a chaperone protein that facilitates export of secreted and transmembrane proteins from the endoplasmic reticulum and plays a role in mitochondrial respiratory chain assembly. Mutations cause X-linked recessive deafness, dystonia, and cerebral hypomyelination, affecting the auditory, motor, and central nervous systems. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.65), and microdeletions involving BCAP31 are associated with contiguous ABCD1/DXS1375E deletion syndrome presenting in the neonatal period.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the B-cell receptor associated protein 31 superfamily. The encoded protein is a multi-pass transmembrane protein of the endoplasmic reticulum that is involved in the anterograde transport of membrane proteins from the endoplasmic reticulum to the Golgi and in caspase 8-mediated apoptosis. Microdeletions in this gene are associated with contiguous ABCD1/DXS1375E deletion syndrome (CADDS), a neonatal disorder. Alternative splicing of this gene results in multiple transcript variants. Two related pseudogenes have been identified on chromosome 16. [provided by RefSeq, Jan 2012]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.65

Clinical Summary— BCAP31

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Gene-Disease Validity (ClinGen)

severe motor and intellectual disabilities-sensorineural deafness-dystonia syndrome · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.21) despite low pLI — interpret in context.

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ClinVar Variants

17 unique Pathogenic / Likely Pathogenic· 86 VUS of 268 total submissions

Explore recent and relevant literature in Research Assistant →

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?

0.65LOEUF

pLI 0.434

Z-score 2.29

OE 0.21 (0.08–0.65)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.30Z-score

OE missense 0.67 (0.56–0.80)

82 obs / 122.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.21 (0.08–0.65)

0≤0.351.4

Missense OE?0.67 (0.56–0.80)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 2 / 9.7Missense obs/exp: 82 / 122.5Syn Z: 0.14

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveBCAP31-related deafness, dystonia, and central hypomyelination with disorganization of the Golgi apparatusLOFXLR

This gene — mechanism propensity

0.7326th %ile

GOF

0.5857th %ile

LOF

0.3355th %ile

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). The Badonyi & Marsh model scores dominant-negative highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOF76% of P/LP variants are LoF · ClinGen HI: Sufficient evidence for dosage pathogenicity

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

268 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12

Likely Pathogenic5

VUS86

Likely Benign89

Benign25

Conflicting10

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	9	0	3	0	12
Likely Pathogenic	4	1	0	0	5
VUS	2	73	10	1	86
Likely Benign	1	7	42	39	89
Benign	2	1	19	3	25
Conflicting	—				10
Total	18	82	74	43	227

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

134 pathogenic / likely-pathogenic (of 156) ClinVar copy-number / structural variants overlap BCAP31 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →