MINDY1

Chr 1

MINDY lysine 48 deubiquitinase 1

Also known as: FAM63A, MINDY-1

NCBI Gene: 55793 ENSG00000143409 UniProt: Q8N5J2 OMIM: 618407

Enables K48-linked deubiquitinase activity; K48-linked polyubiquitin modification-dependent protein binding activity; and cysteine-type carboxypeptidase activity. Predicted to be involved in proteolysis. Located in nuclear body. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.28

Clinical Summary— MINDY1

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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

74 VUS of 100 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?

1.28LOEUF

pLI 0.000

Z-score 0.42

OE 0.91 (0.67–1.28)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.21Z-score

OE missense 0.80 (0.72–0.89)

233 obs / 291.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.91 (0.67–1.28)

0≤0.351.4

Missense OE?0.80 (0.72–0.89)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 25 / 27.4Missense obs/exp: 233 / 291.2Syn Z: -1.26

This gene — mechanism propensity

0.6162th %ile

GOF

0.6540th %ile

LOF

0.2483th %ile

The highest-scoring mechanism for this gene is gain-of-function.

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

100 submitted variants in ClinVar

ClinVar

Classification Summary

VUS74

Likely Benign4

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	64	8	1	74
Likely Benign	0	3	0	1	4
Benign	0	0	0	0	0
Total	1	67	8	2	78

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

View in ClinVar →

15 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap MINDY1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →