NEXMIF

Chr XXLD

neurite extension and migration factor

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

NCBI Gene: 340533ENSG00000050030UniProt: Q5QGS0OMIM: 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.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
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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ClinVar Variants
46 unique Pathogenic / Likely Pathogenic· 140 VUS of 300 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

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 OE0.06 (0.03–0.20)
0≤0.351.4
Missense OE0.85 (0.78–0.92)
0≤0.61.4
Synonymous OE1.03
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
DN
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 · 80% of P/LP variants are LoF · LOEUF 0.20

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

ClinVar Variant Classifications

300 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic11
VUS140
Likely Benign35
Benign4
35
Pathogenic
11
Likely Pathogenic
140
VUS
35
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
27
0
8
0
35
Likely Pathogenic
10
0
1
0
11
VUS
0
137
3
0
140
Likely Benign
0
8
1
26
35
Benign
0
2
1
1
4
Total371471427225

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

View in ClinVar →

Protein Context — Lollipop Plot

NEXMIF · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Intellectual disorder type 98 caused by a novel NEXMIF variant: a case report and literature review.
Zhu Y et al.·Front Med (Lausanne)
2026Open AccessReview
A rare GCH1 p.Arg170Gly variant shows impaired enzymatic activity and co-occurs with a novel NEXMIF p.Asp155GlnfsTer2 leading to a complex neurological phenotype: functional studies and clinical aspects.
Ślusarczyk K et al.·Mol Genet Metab
2026Functional
Restoration of NEXMIF expression rescues abnormalities in gene transcription, neuron maturation and autistic-like behaviors in Nexmif knockout mice.
Odamah K et al.·Transl Psychiatry
2025Open Access
NEXMIF overexpression is associated with autism-like behaviors and alterations in dendritic arborization and spine formation in mice.
Odamah K et al.·Front Neurosci
2025Open Access
KIAA2022/NEXMIF c.1882C>T (p.Arg628*) Variant in a Romanian Patient with Neurodevelopmental Disorders and Epilepsy: A Case Report and Systematic Review.
Anastasescu CM et al.·Life (Basel)
2025Open AccessReview
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients