MYCBP2

Chr 13

MYC binding protein 2

Also known as: Myc-bp2, PAM, PHR1, Phr

The protein functions as an atypical E3 ubiquitin ligase that ubiquitinates threonine and serine residues on target proteins and plays a key role in neural development by regulating neurite outgrowth, synaptic growth, axon guidance, and axon degeneration. Mutations cause inherited vision defects with an autosomal dominant inheritance pattern. MYCBP2 is highly constrained against loss-of-function mutations, indicating that haploinsufficiency is likely not tolerated in the general population.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.12
Clinical SummaryMYCBP2
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
18 unique Pathogenic / Likely Pathogenic· 399 VUS of 499 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.12LOEUF
pLI 1.000
Z-score 13.05
OE 0.08 (0.050.12)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
6.05Z-score
OE missense 0.65 (0.630.68)
1566 obs / 2399.2 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios
LoF OE0.08 (0.050.12)
00.351.4
Missense OE0.65 (0.630.68)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 18 / 232.8Missense obs/exp: 1566 / 2399.2Syn Z: 0.01
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedMYCBP2-related developmental delay with corpus callosum defectsOTHERAD
DN
0.2798th %ile
GOF
0.2398th %ile
LOF
0.82top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 61% of P/LP variants are LoF · LOEUF 0.12

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

499 submitted variants in ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic6
VUS399
Likely Benign5
Conflicting1
12
Pathogenic
6
Likely Pathogenic
399
VUS
5
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
2
4
0
12
Likely Pathogenic
5
1
0
0
6
VUS
4
388
7
0
399
Likely Benign
0
2
0
3
5
Benign
0
0
0
0
0
Conflicting
1
Total15393113423

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

View in ClinVar →

Protein Context — Lollipop Plot

MYCBP2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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