ZFP91

Chr 11

ZFP91 zinc finger protein, atypical E3 ubiquitin ligase

Also known as: DMS-8, DSM-8, DSM8, FKSG11, PZF, ZFP-91, ZNF757

NCBI Gene: 80829 ENSG00000186660 UniProt: Q96JP5 OMIM: 619289

The protein encoded by this gene is a member of the zinc finger family of proteins. The gene product contains C2H2-type domains, which are the classical zinc finger domains found in numerous nucleic acid-binding proteins. This protein functions as a regulator of the non-canonical NF-kappaB pathway in lymphotoxin-beta receptor signaling. Alternative splicing results in multiple transcript variants. A read-through transcript variant composed of ZFP91 and the downstream CNTF gene sequence has been identified, but it is thought to be non-coding. Read-through transcription of ZFP91 and CNTF has also been observed in mouse. A ZFP91-related pseudogene has also been identified on chromosome 2. [provided by RefSeq, Oct 2010]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.17

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.17LOEUF

pLI 1.000

Z-score 4.69

OE 0.04 (0.01–0.17)

Highly constrained

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

Missense Constraint?

1.63Z-score

OE missense 0.73 (0.65–0.82)

215 obs / 293.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.04 (0.01–0.17)

0≤0.351.4

Missense OE?0.73 (0.65–0.82)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 1 / 27.6Missense obs/exp: 215 / 293.6Syn Z: -0.92

Background carrier burden — how many people carry a rare variant somewhere in ZFP91?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

670 rare PASS variants

Rare truncating (LoF)

1 in 10,000

30 rare PASS variants

Rare synonymous (reference)

1 in 160

353 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZFP91. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 220	1 in 13,000
South Asian	~43k	1 in 120	≈ 1 in 17,000
Remaining (unassigned)	~30k	1 in 89	≈ 1 in 9,200
European (Finnish)	~27k	1 in 420	≈ 1 in 6,500
Admixed American	~22k	1 in 84	1 in 2,900
African / African American	~21k	1 in 57	≈ 1 in 8,000
East Asian	~20k	1 in 86	1 in 1,500
Ashkenazi Jewish	~13k	1 in 680	none seen
Middle Eastern	~2,884	1 in 77	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 9 of 11 coding exons well covered in gnomAD exomes; exons 1, 2 marginal. Genomes: all 11.? see exons ↓