BCORL1

protein-coding

BCL6 corepressor like 1, the group of Ankyrin repeat domain containing

Gene summary

The protein encoded by this gene is a transcriptional corepressor that is found tethered to promoter regions by DNA-binding proteins. The encoded protein can interact with several different class II histone deacetylases to repress transcription. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

Previous symbols:

CXorf10

MANE transcript

NM_001379451.1

Inheritance

XL, AD

ClinVar variants

P:7U:639B:113

Top phenotype

Shukla-Vernon syndrome

gnomAD constraint

pLI —, LoF o/e 0.05

Max pathogenic AF

—

Genomic locus

chrX:129,981,107-130,058,071

External References & Databases

Ensembl (ENSG00000085185)

Transcript & Mutation Effects

hg38 • Region Span ~77.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Shukla-Vernon syndromeLIMITED

Inheritance Pattern: XL

Disease ID:MONDO:0026727

Submitter: ClinGen

*BCORL1* was first reported in relation to the X-linked recessive neurodevelopmental disorder Shukla-Vernon syndrome in 2019 (Shukla et al., PMID: 30941876). Eight missense variants that have been reported in 13 probands in 5 publications (PMIDs: 30941876, 24121876, 23849776, 33810051, 34400773) are included in this curation. The mechanism of pathogenicity is unknown. Affected individuals present with global developmental delay, variably impaired intellectual development, and behavioral abnormalities, including autism spectrum disorder and attention deficit hyperactivity disorder. Dysmorphic features are common and may include tall forehead, downslanting palpebral fissures, and tapering fingers. Some patients may have seizures and/or cerebellar atrophy on brain imaging. Carrier mothers may have mild manifestations, including learning disabilities. In summary, there is limited evidence to support the relationship between *BCORL1* and Shukla-Vernon syndrome. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen Intellectual Disability and Autism GCEP on the meeting date March 5th, 2024 (SOP Version 10).

Shukla-Vernon syndromeSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0026727

Submitter: Labcorp Genetics (formerly Invitae)

Shukla-Vernon syndromeLIMITED

Inheritance Pattern: XL

Disease ID:MONDO:0026727

Submitter: Ambry Genetics

Shukla-Vernon syndromeLIMITED

Inheritance Pattern: XL

Disease ID:MONDO:0026727

Submitter: Illumina

syndromic intellectual disabilitySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0000508

Submitter: Orphanet

Shukla-Vernon syndromeLIMITED

Inheritance Pattern: XL

Disease ID:MONDO:0026727

Submitter: G2P

congenital anomaly of kidney and urinary tractMODERATE

Inheritance Pattern: XL

Disease ID:MONDO:0019719

Submitter: PanelApp Australia

Shukla-Vernon syndromeMODERATE

Inheritance Pattern: XL

Disease ID:MONDO:0026727

Submitter: PanelApp Australia

spermatogenic failureSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0004983

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Shukla-Vernon syndromeXL

Manifestation: Craniofacial; Musculoskeletal; 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: 24123876; 30941876

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BCORL1 variants in ClinVar

11 Conditions Cataloged

not providedTotal: 318

not specifiedTotal: 165

Shukla-Vernon syndromeTotal: 66

BCORL1-related disorderTotal: 43

See casesTotal: 3

OligoasthenoteratozoospermiaTotal: 2

Multiple myelomaTotal: 1

Neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001379451.1. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			58 clinvar	62 clinvar	11 clinvar	131
missense	2 clinvar	2 clinvar	512 clinvar	39 clinvar	1 clinvar	556
nonsense	1 clinvar	1 clinvar	25 clinvar			27
start loss						0
frameshift		1 clinvar	14 clinvar			15
splice donor/acceptor (+/-2bp)			30 clinvar			30
Total	3	4	639	101	12	759

Highest pathogenic variant AF is 0.00008525424

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001379451.1	RefSeq	NP_001366380.1	13	MANE Select
ENST00000540052.6	Ensembl	ENSP00000437775.2	13	MANE Select
NM_001184772.3	RefSeq	NP_001171701.1	13	Standard
NM_001379450.1	RefSeq	NP_001366379.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Mesodermal Commitment Pathway
Pathways Affected in Adenoid Cystic Carcinoma

Biological Process

chromatin organization

Cellular Component

nucleoplasm
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000540052
Coding exons: 12
Length: 76976
Individuals with no LoFs: 125697
Homozygous LoFs: 5
Heterozygous LoFs: 6
Defined: 125708
p: 0.0000438

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.06	581	739	0.786	0.0000624	10997
Missense (PolyPhen)		124	222.97	0.55613		3368
Synonymous	1.02	302	325	0.928	0.0000297	3783
Loss of Function	5.67	2	41.4	0.0483	0.00000350	623

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000077	0.000062	rare
Latino/Admixed American	0.00015	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00058	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000013	0.0000088	rare
South Asian	0	0.0	absent
Other	0.00025	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional corepressor. May specifically inhibit gene expression when recruited to promoter regions by sequence- specific DNA-binding proteins such as BCL6. This repression may be mediated at least in part by histone deacetylase activities which can associate with this corepressor. {ECO:0000269|PubMed:17379597}.;

Recessive Scores

pRec: 0.105

Intolerance Scores

LoFtool: 0.338
RVIS EVS: -2.12
RVIS percentile EVS: 1.52

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.670

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium