CD2BP2

Chr 16

CD2 cytoplasmic tail binding protein 2

Also known as: FWP010, LIN1, PPP1R59, Snu40, U5-52K

NCBI Gene: 10421 ENSG00000169217 UniProt: O95400 OMIM: 604470

The protein functions as a component of the U5 small nuclear ribonucleoprotein complex involved in pre-mRNA splicing and also regulates T lymphocyte activation by binding to the CD2 surface antigen. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, refractory seizures, and progressive microcephaly. The gene shows tolerance to loss-of-function variants with a low constraint score.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a bi-functional protein. In the cytoplasm, the encoded protein binds the cytoplasmic tail of human surface antigen CD2 via its C-terminal GYF domain, and regulate CD2-triggered T lymphocyte activation. In the nucleus, this protein is a component of the U5 small nuclear ribonucleoprotein complex and is involved in RNA splicing. A pseudogene has been identified on chromosome 7. Alternative splicing results in multiple transcript variants but their biological validity has not been determined. [provided by RefSeq, Nov 2008]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.04

Clinical Summary— CD2BP2

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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

58 VUS of 70 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?

1.04LOEUF

pLI 0.000

Z-score 1.46

OE 0.61 (0.38–1.04)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.56Z-score

OE missense 1.11 (0.99–1.24)

233 obs / 210.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.61 (0.38–1.04)

0≤0.351.4

Missense OE?1.11 (0.99–1.24)

0≤0.61.4

Synonymous OE?1.40

0≤1.21.6

LoF obs/exp: 10 / 16.4Missense obs/exp: 233 / 210.2Syn Z: -2.88

This gene — mechanism propensity

0.6454th %ile

GOF

0.4973th %ile

LOF

0.3452th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

70 submitted variants in ClinVar

ClinVar

Classification Summary

VUS58

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	58	58
Likely Benign	2	2
Benign	0	0
Total	60	60

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

View in ClinVar →

16 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap CD2BP2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →