NEXMIF

Chr XXLD

neurite extension and migration factor

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

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]

OMIMResearchGenerating clinical summary…
LOFmechanismXLDLOEUF 0.201 OMIM phenotype
Clinical SummaryNEXMIF
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Gene-Disease Validity (ClinGen)
X-linked complex neurodevelopmental disorder · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

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
214 unique Pathogenic / Likely Pathogenic· 606 VUS of 1326 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint?
0.20LOEUF
pLI 1.000
Z-score 4.90
OE 0.06 (0.030.20)
Highly constrained

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

Missense Constraint?
1.27Z-score
OE missense 0.85 (0.780.92)
464 obs / 547.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.06 (0.030.20)
00.351.4
Missense OE?0.85 (0.780.92)
00.61.4
Synonymous OE?1.03
01.21.6
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

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 · 98% of P/LP variants are LoF · 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.

ClinVar Variant Classifications

1326 submitted variants in ClinVar

Classification Summary

Pathogenic183
Likely Pathogenic31
VUS606
Likely Benign305
Benign50
Conflicting63
183
Pathogenic
31
Likely Pathogenic
606
VUS
305
Likely Benign
50
Benign
63
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
182
0
1
0
183
Likely Pathogenic
27
1
3
0
31
VUS
4
593
6
3
606
Likely Benign
1
71
15
218
305
Benign
0
32
1
17
50
Conflicting
63
Total214697262381,238

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

View in ClinVar →

64 pathogenic / likely-pathogenic (of 74) ClinVar copy-number / structural variants overlap NEXMIF — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

NEXMIF · protein map & ClinVar variants

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