ZHX1-C8ORF76

Chr 8

ZHX1-C8orf76 readthrough

NCBI Gene: 100533106 ENSG00000259305 UniProt: Q96EF9

The ZHX1-C8ORF76 fusion protein results from natural read-through transcription between two neighboring genes and contains a distinct N-terminus from ZHX1 combined with C8ORF76 sequence. This gene is extremely tolerant to loss-of-function variants based on population data, and no definitive disease associations have been established for mutations in this fusion transcript. The clinical significance of variants in this read-through gene remains uncertain.

ResearchSummary from RefSeq

This locus represents naturally occurring read-through transcription between the neighboring zinc fingers and homeoboxes 1 (ZHX1) and chromosome 8 open reading frame 76 (C8orf76) genes. The read-through transcript encodes a protein that shares sequence identity with the downstream gene, but it has a distinct N-terminus encoded by exon structure from the upstream gene. [provided by RefSeq, Feb 2011]

ResearchGenerating clinical summary…

LOEUF 1.51

Clinical Summary— ZHX1-C8ORF76

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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

98 VUS of 106 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?

1.51LOEUF

pLI 0.000

Z-score 0.10

OE 0.97 (0.64–1.51)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.04Z-score

OE missense 0.99 (0.86–1.14)

143 obs / 144.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.97 (0.64–1.51)

0≤0.351.4

Missense OE?0.99 (0.86–1.14)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 14 / 14.4Missense obs/exp: 143 / 144.3Syn Z: 0.14

ClinVar Variant Classifications

106 submitted variants in ClinVar

ClinVar

Classification Summary

VUS98

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	98	0	98
Likely Benign	1	1	2
Benign	0	0	0
Total	99	1	100

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

View in ClinVar →

49 pathogenic / likely-pathogenic (of 50) ClinVar copy-number / structural variants overlap ZHX1-C8ORF76 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →