DUSP14

Chr 17

dual specificity phosphatase 14

Also known as: MKP-L, MKP6

NCBI Gene: 11072 ENSG00000276023 UniProt: O95147 OMIM: 606618

The protein is a dual-specificity phosphatase that inactivates MAP kinases (ERK, JNK, and p38) and negatively regulates T-cell receptor signaling by dephosphorylating the MAP3K7 adapter TAB1. This gene is not highly constrained against loss-of-function variants. No human diseases have been definitively associated with mutations in DUSP14 based on the provided information.

OMIM ResearchSummary from RefSeq, UniProt

Dual-specificity phosphatases (DUSPs) constitute a large heterogeneous subgroup of the type I cysteine-based protein-tyrosine phosphatase superfamily. DUSPs are characterized by their ability to dephosphorylate both tyrosine and serine/threonine residues. They have been implicated as major modulators of critical signaling pathways. DUSP14 contains the consensus DUSP C-terminal catalytic domain but lacks the N-terminal CH2 domain found in the MKP (mitogen-activated protein kinase phosphatase) class of DUSPs (see MIM 600714) (summary by Patterson et al., 2009 [PubMed 19228121]).[supplied by OMIM, Dec 2009]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.17

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.17LOEUF

pLI 0.121

Z-score 1.35

OE 0.37 (0.15–1.17)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.45Z-score

OE missense 0.64 (0.53–0.77)

82 obs / 128.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.37 (0.15–1.17)

0≤0.351.4

Missense OE?0.64 (0.53–0.77)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 2 / 5.4Missense obs/exp: 82 / 128.2Syn Z: 0.51

Background carrier burden — how many people carry a rare variant somewhere in DUSP14?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

200 rare PASS variants

Rare truncating (LoF)

1 in 11,000

23 rare PASS variants

Rare synonymous (reference)

1 in 290

97 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DUSP14. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 270	1 in 9,600
South Asian	~43k	1 in 450	≈ 1 in 43,000
Remaining (unassigned)	~30k	1 in 200	≈ 1 in 10,000
European (Finnish)	~27k	1 in 480	≈ 1 in 27,000
Admixed American	~22k	1 in 280	≈ 1 in 22,000
African / African American	~21k	1 in 250	≈ 1 in 9,300
East Asian	~20k	1 in 370	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 730	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 210	≈ 1 in 960

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓