MOB3C

Chr 1

MOB kinase activator 3C

Also known as: MOB1E, MOBKL2C

NCBI Gene: 148932 ENSG00000142961 UniProt: Q70IA8 OMIM: 620804

The encoded protein may regulate kinase activity and is similar to yeast Mob1, which is involved in spindle pole body duplication and mitotic checkpoint regulation. The gene is not highly constrained against loss-of-function variants (pLI = 0.00002, LOEUF = 1.21), and no established disease associations are documented in the provided data.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is similar to the yeast Mob1 protein. Yeast Mob1 binds Mps1p, a protein kinase essential for spindle pole body duplication and mitotic checkpoint regulation. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.21

Clinical Summary— MOB3C

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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

53 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?

1.21LOEUF

pLI 0.000

Z-score 1.02

OE 0.70 (0.42–1.21)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.64Z-score

OE missense 0.87 (0.77–0.99)

169 obs / 194.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.70 (0.42–1.21)

0≤0.351.4

Missense OE?0.87 (0.77–0.99)

0≤0.61.4

Synonymous OE?0.73

0≤1.21.6

LoF obs/exp: 9 / 12.9Missense obs/exp: 169 / 194.0Syn Z: 1.87

This gene — mechanism propensity

0.6549th %ile

GOF

0.7126th %ile

LOF

0.2678th %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

VUS53

Likely Benign2

VUS

Likely 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	51	2	53
Likely Benign	0	2	2
Benign	0	0	0
Total	51	4	55

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

View in ClinVar →

6 pathogenic / likely-pathogenic (of 10) ClinVar copy-number / structural variants overlap MOB3C — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →