BCAM

protein-coding

basal cell adhesion molecule (Lutheran blood group), the group of CD molecules|C2-set domain containing|Ig-like cell adhesion molecule family|Blood group antigens

Gene summary

This gene encodes Lutheran blood group glycoprotein, a member of the immunoglobulin superfamily and a receptor for the extracellular matrix protein, laminin. The protein contains five extracellular immunoglobulin domains, a single transmembrane domain, and a short C-terminal cytoplasmic tail. This protein may play a role in epithelial cell cancer and in vaso-occlusion of red blood cells in sickle cell disease. Polymorphisms in this gene define some of the antigens in the Lutheran system and also the Auberger system. Inactivating variants of this gene result in the recessive Lutheran null phenotype, Lu(a-b-), of the Lutheran blood group. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

Previous symbols:

MANE transcript

NM_005581.5

Inheritance

ClinVar variants

P:4U:119B:21

Top phenotype

Blood group, Lutheran system; Blood group, Auberger system; Blood group, Lutheran null

gnomAD constraint

pLI —, LoF o/e 0.56

Max pathogenic AF

—

Genomic locus

chr19:44,809,071-44,821,421

External References & Databases

Ensembl (ENSG00000187244)

Transcript & Mutation Effects

hg38 • Region Span ~12.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

Clinical Genomic Database (CGD)

Blood group, Lutheran system; Blood group, Auberger system; Blood group, Lutheran nullBG

Manifestation: Hematologic

Intervention: Hematologic

Rationale: Variants associated with a blood group may be important in specific situations (eg, related to transfusion)

Refs: 14025138; 4836779; 1146276; 9192786; 9166867; 17319831; 18487511

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BCAM variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 114

BCAM-related disorderTotal: 11

not providedTotal: 10

BLOOD GROUP--LUTHERAN NULLTotal: 3

BLOOD GROUP--LUTHERAN SYSTEMTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005581.5. 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			2 clinvar	6 clinvar	3 clinvar	11
missense			111 clinvar	10 clinvar	2 clinvar	123
nonsense	3 clinvar					3
start loss						0
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	3	1	119	16	5	144

Highest pathogenic variant AF is 0.000004341403

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005581.5	RefSeq	NP_005572.2	15	MANE Select
ENST00000270233.12	Ensembl	ENSP00000270233.5	15	MANE Select
NM_001013257.2	RefSeq	NP_001013275.1	13	Standard
ENST00000590196.1	Ensembl	ENSP00000468189.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cell adhesion
cell-matrix adhesion
signal transduction

Molecular Function

transmembrane signaling receptor activity
laminin receptor activity
protein binding
protein C-terminus binding
laminin binding

Cellular Component

extracellular region
plasma membrane
integral component of plasma membrane
external side of plasma membrane
collagen-containing extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000270233
Coding exons: 15
Length: 12346
Individuals with no LoFs: 125690
Homozygous LoFs: 1
Heterozygous LoFs: 53
Defined: 125744
p: 0.000215

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.253	402	417	0.965	0.0000295	3966
Missense (PolyPhen)		138	148.81	0.92737		1383
Synonymous	-0.454	191	183	1.04	0.0000140	1346
Loss of Function	2.29	18	32.0	0.563	0.00000180	328

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00023	0.00022	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00028	0.00026	rare
South Asian	0.00026	0.00026	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Laminin alpha-5 receptor. May mediate intracellular signaling. {ECO:0000269|PubMed:9616226}.;

Recessive Scores

pRec: 0.160

Intolerance Scores

LoFtool: 0.674
RVIS EVS: 1.25
RVIS percentile EVS: 93.48

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.717

Gene Damage Prediction

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