ERMAP

Chr 1

erythroblast membrane associated protein (Scianna blood group)

Also known as: BTN5, PRO2801, RD, SC

NCBI Gene: 114625 ENSG00000164010 UniProt: Q96PL5 OMIM: 609017

The protein encoded by ERMAP is a cell surface transmembrane protein that functions as an erythroid cell receptor and mediates cell adhesion. Mutations in this gene are responsible for polymorphisms in the Scianna/Radin blood group system. The gene shows very low constraint against loss-of-function variants, consistent with its role in blood group determination rather than essential cellular functions.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a cell surface transmembrane protein that may act as an erythroid cell receptor, possibly as a mediator of cell adhesion. Polymorphisms in this gene are responsible for the Scianna/Radin blood group system. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.172 OMIM phenotypes

Clinical Summary— ERMAP

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 59 VUS of 86 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.17LOEUF

pLI 0.000

Z-score 0.96

OE 0.78 (0.53–1.17)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.71Z-score

OE missense 0.88 (0.79–0.98)

234 obs / 266.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.78 (0.53–1.17)

0≤0.351.4

Missense OE?0.88 (0.79–0.98)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 17 / 21.9Missense obs/exp: 234 / 266.4Syn Z: 0.23

This gene — mechanism propensity

0.7325th %ile

GOF

0.72top 25%

LOF

0.2679th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction 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.

ClinVar Variant Classifications

86 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS59

Likely Benign7

Benign6

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	0	0	1
Likely Pathogenic	0	0	0	0	0
VUS	0	59	0	0	59
Likely Benign	0	4	0	3	7
Benign	0	3	1	2	6
Total	1	66	1	5	73

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

View in ClinVar →

12 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap ERMAP — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →