DUSP12

Chr 1

dual specificity phosphatase 12

Also known as: DUSP1, YVH1

NCBI Gene: 11266 ENSG00000081721 UniProt: Q9UNI6 OMIM: 604835

The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which is associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene product is the human ortholog of the Saccharomyces cerevisiae YVH1 protein tyrosine phosphatase. It is localized predominantly in the nucleus, and is novel in that it contains, and is regulated by a zinc finger domain. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.89

Clinical Summary— DUSP12

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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

51 VUS of 61 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.89LOEUF

pLI 0.000

Z-score 1.90

OE 0.51 (0.31–0.89)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.58Z-score

OE missense 0.88 (0.78–1.00)

169 obs / 191.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.51 (0.31–0.89)

0≤0.351.4

Missense OE?0.88 (0.78–1.00)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 9 / 17.6Missense obs/exp: 169 / 191.6Syn Z: 0.60

This gene — mechanism propensity

0.6841th %ile

GOF

0.6637th %ile

LOF

0.2580th %ile

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

DNprediction above median

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

61 submitted variants in ClinVar

ClinVar

Classification Summary

VUS51

Likely Benign4

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	51	51
Likely Benign	4	4
Benign	0	0
Total	55	55

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

View in ClinVar →

13 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap DUSP12 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →