CD200R1

Chr 3

CD200 receptor 1

Also known as: CD200R, HCRTR2, MOX2R, OX2R

NCBI Gene: 131450 ENSG00000163606 UniProt: Q8TD46 OMIM: 607546

CD200R1 encodes an inhibitory receptor that binds CD200 and suppresses inflammatory responses by limiting pro-inflammatory cytokine production in myeloid cells. Mutations cause autosomal recessive primary immunodeficiency with recurrent infections, chronic diarrhea, and colitis typically presenting in infancy. This gene is not highly constrained against loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a receptor for the OX-2 membrane glycoprotein. Both the receptor and substrate are cell surface glycoproteins containing two immunoglobulin-like domains. This receptor is restricted to the surfaces of myeloid lineage cells and the receptor-substrate interaction may function as a myeloid downregulatory signal. Mouse studies of a related gene suggest that this interaction may control myeloid function in a tissue-specific manner. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.37

Clinical Summary— CD200R1

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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

44 VUS of 57 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?

1.37LOEUF

pLI 0.000

Z-score 0.47

OE 0.87 (0.58–1.37)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.70Z-score

OE missense 0.85 (0.75–0.97)

157 obs / 183.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.87 (0.58–1.37)

0≤0.351.4

Missense OE?0.85 (0.75–0.97)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 14 / 16.0Missense obs/exp: 157 / 183.8Syn Z: 0.11

This gene — mechanism propensity

0.7131th %ile

GOF

0.77top 25%

LOF

0.2775th %ile

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

GOFprediction above median

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.

ClinVar Variant Classifications

57 submitted variants in ClinVar

ClinVar

Classification Summary

VUS44

Likely Benign4

Benign3

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	44	0	44
Likely Benign	4	0	4
Benign	2	1	3
Total	50	1	51

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

View in ClinVar →

28 pathogenic / likely-pathogenic (of 32) ClinVar copy-number / structural variants overlap CD200R1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →