GeneBe

BCAP31

protein-coding

B cell receptor associated protein 31

Gene summary

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]

MANE transcript

NM_001256447.2

Inheritance

XL, AR

ClinVar variants

P:14U:102B:54

Top phenotype

Deafness, dystonia, and cerebral hypomyelination

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chrX:153,700,492-153,724,565

External References & Databases

Ensembl (ENSG00000185825)NCBI Gene (10134)OMIM (300398)HGNC:16695GenCCUniProt (P51572)AlphaFoldClinVar (BCAP31)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~24.1 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

severe motor and intellectual disabilities-sensorineural deafness-dystonia syndromeDEFINITIVE

Inheritance Pattern: XL

Disease ID:MONDO:0010334

Submitter: ClinGen

*BCAP31* was first reported in relation to X-linked severe motor and intellectual disabilities-sensorineural deafness-dystonia syndrome in 2013 (Cacciagli et al., PMID: 24011989). Phenotypic features reported in affected male probands include severe motor and language delays, intellectual disability, sensorineural hearing loss, dystonia, and central hypomyelination. Carrier females display variable phenotypes including sensorineural hearing loss and, in females with skewed X-inactivation, a more severe presentation with intellectual disability, central hypomyelination, hearing loss, and motor delay. Twenty-one variants (2 missense, 1 in-frame indel, 8 frameshift, 4 nonsense, 4 canonical splice site, 1 partial gene deletion, and 1 start loss) reported in 23 probands (21 male and 2 female with skewed X-inactivation), in 9 publications (PMIDs: 19344873, 24011989, 28332767, 30713915, 31330203, 31953925, 32652807, 32681719, 33603160) are included in this curation. The mechanism of pathogenicity appears to be loss of function. More evidence is available in the literature, but the maximum score for genetic evidence (12 points) has been reached. *BCAP31* encodes BAP31, a chaperone protein of the endoplasmic reticulum that plays a role in regulation of protein transport, degradation, and apoptosis. This gene-disease relationship is also supported by functional alteration in patient cells. Fibroblasts from affected individuals exhibited larger size and an increased likelihood of exhibiting disorganized Golgi morphology in comparison to control fibroblasts (PMID: 24011989). In summary, there is definitive evidence supporting the relationship between *BCAP31* and X-linked severe motor and intellectual disabilities-sensorineural deafness-dystonia syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on August 2, 2023 (SOP Version 9).

severe motor and intellectual disabilities-sensorineural deafness-dystonia syndromeSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010334

Submitter: PanelApp Australia

severe motor and intellectual disabilities-sensorineural deafness-dystonia syndromeSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010334

Submitter: Labcorp Genetics (formerly Invitae)

severe motor and intellectual disabilities-sensorineural deafness-dystonia syndromeDEFINITIVE

Inheritance Pattern: XL

Disease ID:MONDO:0010334

Submitter: G2P

severe motor and intellectual disabilities-sensorineural deafness-dystonia syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0010334

Submitter: Orphanet

Clinical Genomic Database (CGD)

Deafness, dystonia, and cerebral hypomyelinationXL

Manifestation: Audiologic/Otolaryngologic; Craniofacial; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 24011989Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BCAP31 variants in ClinVar

8 Conditions Cataloged
not providedTotal: 178
Inborn genetic diseasesTotal: 27
Severe motor and intellectual disabilities-sensorineural deafness-dystonia syndromeTotal: 14
BCAP31-related disorderTotal: 10
not specifiedTotal: 5
SeizureTotal: 1
Global developmental delayTotal: 1
MicrocephalyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001256447.2. 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.

EffectPLPVUSLBBSum
synonymous
4
clinvar
38
clinvar
3
clinvar
 45
missense
1
clinvar
81
clinvar
12
clinvar
1
clinvar
 95
nonsense
5
clinvar
1
clinvar
3
clinvar
 9
start loss
0
frameshift
3
clinvar
1
clinvar
2
clinvar
 6
splice donor/acceptor (+/-2bp)
2
clinvar
1
clinvar
12
clinvar
 15
Total104102504170
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 59 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001256447.2RefSeqNP_001243376.17MANE Select
ENST00000345046.12EnsemblENSP00000343458.67MANE Select
NM_001139441.1RefSeqNP_001132913.17Standard
NM_001139457.2RefSeqNP_001132929.18Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Protein processing in endoplasmic reticulum - Homo sapiens (human)
  • Human papillomavirus infection - Homo sapiens (human)
  • Apoptotic cleavage of cellular proteins
  • Apoptotic execution phase
  • Apoptosis

Biological Process

  • antigen processing and presentation of peptide antigen via MHC class I
  • intracellular protein transport
  • endoplasmic reticulum to Golgi vesicle-mediated transport
  • apoptotic process
  • positive regulation of cytosolic calcium ion concentration

Molecular Function

  • protein binding
  • MHC class I protein binding
  • protein-containing complex binding

Cellular Component

  • mitochondrion
  • endoplasmic reticulum
  • Sec61 translocon complex
  • endoplasmic reticulum membrane
  • lipid droplet

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000458587
Coding exons
8
Length
24206
Individuals with no LoFs
0
Homozygous LoFs
0
Heterozygous LoFs
0
Defined
0
p
0.00
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.30821230.6690.000009772024
Missense (PolyPhen)2249.5240.44423768
Synonymous0.1365354.30.9760.00000454626
Loss of Function2.2929.690.2066.11e-7189

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)00.0absent
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Functions as a chaperone protein. Is one of the most abundant endoplasmic reticulum (ER) proteins. Plays a role in the export of secreted proteins in the ER, the recognition of abnormally folded protein and their targeting to the ER associated-degradation (ERAD). Also serves as a cargo receptor for the export of transmembrane proteins. May be involved in CASP8- mediated apoptosis. {ECO:0000269|PubMed:10958671, ECO:0000269|PubMed:18287538, ECO:0000269|PubMed:9396746}.;
Disease
DISEASE: Deafness, dystonia, and cerebral hypomyelination (DDCH) [MIM:300475]: An X-linked recessive mental retardation syndrome characterized by almost no psychomotor development, dysmorphic facial features, sensorineural deafness, dystonia, pyramidal signs, and hypomyelination on brain imaging. {ECO:0000269|PubMed:24011989}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=BCAP31 is deleted in the chromosome Xq28 deletion syndrome which involves BCAP31 and the and the promoter region of ABCD1. {ECO:0000269|PubMed:11992258}.;

Recessive Scores

pRec
0.169

Intolerance Scores

RVIS EVS
-0.01
RVIS percentile EVS
53.19

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.539

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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