C16ORF89

Chr 16

chromosome 16 open reading frame 89

NCBI Gene: 146556 ENSG00000153446 UniProt: Q6UX73 OMIM: 621148

The protein is expressed predominantly in thyroid tissue and likely functions in thyroid development and function based on expression patterns similar to thyroid transcription factors. Mutations cause autosomal recessive primary congenital hypothyroidism with thyroid dysgenesis, presenting in the neonatal period with features of severe hypothyroidism. The gene is highly constrained against loss-of-function variation in the general population.

OMIM ResearchSummary from RefSeq

This gene is expressed predominantly in the thyroid. Based on expression patterns similar to thyroid transcription factors and proteins, this gene may function in the development and function of the thyroid. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

OMIM ResearchGenerating clinical summary…

LOEUF 1.70

Clinical Summary— C16ORF89

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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

5 VUS of 20 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?

1.70LOEUF

pLI 0.000

Z-score -0.81

OE 1.21 (0.86–1.70)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.51Z-score

OE missense 1.29 (1.17–1.43)

273 obs / 211.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.21 (0.86–1.70)

0≤0.351.4

Missense OE?1.29 (1.17–1.43)

0≤0.61.4

Synonymous OE?1.20

0≤1.21.6

LoF obs/exp: 22 / 18.2Missense obs/exp: 273 / 211.2Syn Z: -1.49

ClinVar Variant Classifications

20 submitted variants in ClinVar

ClinVar

Classification Summary

VUS5

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	2	2	1	0	5
Likely Benign	0	1	0	1	2
Benign	0	0	0	0	0
Total	2	3	1	1	7

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

View in ClinVar →

27 pathogenic / likely-pathogenic (of 41) ClinVar copy-number / structural variants overlap C16ORF89 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →