NEXMIF

Chr XXLD

neurite extension and migration factor

Also known as: KIAA2022, KIDLIA, MRX98, XLID98, XPN

NCBI Gene: 340533 ENSG00000050030 OMIM: 300524

The NEXMIF protein localizes to the nucleus and mutations cause X-linked intellectual developmental disorder (XLID-98) with an X-linked dominant inheritance pattern. Mutations predominantly cause disease through loss-of-function mechanisms, with the gene showing high intolerance to loss-of-function variants (pLI 0.999, LOEUF 0.198), indicating haploinsufficiency is likely pathogenic.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

An inversion on the X chromosome which disrupts this gene and a G-protein coupled purinergic receptor gene located in the pseudoautosomal region of the X chromosome has been linked to X linked cognitive disability.[provided by RefSeq, Mar 2009]

OMIM ResearchGenerating clinical summary…

LOFmechanismXLDLOEUF 0.201 OMIM phenotype

Clinical Summary— NEXMIF

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Gene-Disease Validity (ClinGen)

X-linked complex neurodevelopmental disorder · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

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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.

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.20LOEUF

pLI 1.000

Z-score 4.90

OE 0.06 (0.03–0.20)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.27Z-score

OE missense 0.85 (0.78–0.92)

464 obs / 547.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.06 (0.03–0.20)

0≤0.351.4

Missense OE?0.85 (0.78–0.92)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 2 / 31.9Missense obs/exp: 464 / 547.8Syn Z: -0.39

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongNEXMIF-related intellectual disability and epilepsy (heterozygous)LOFmonoallelic_X_heterozygous

strongNEXMIF-related intellectual disability and epilepsy (hemizygous)OTHERXLR

This gene — mechanism propensity

0.2698th %ile

GOF

0.3392th %ile

LOF

0.87top 5%

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

LOFprediction above median · LOEUF 0.20 · ClinGen HI: Sufficient evidence for dosage pathogenicity

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