KNOP1

Chr 16

lysine rich nucleolar protein 1

Also known as: 101F10.1, C16orf88, FAM191A, TSG118

NCBI Gene: 400506 ENSG00000103550 UniProt: Q1ED39 OMIM: 621293

KNOP1 encodes a nucleolar protein that interacts with zinc finger 106 protein and may be involved in testis development. Mutations cause autosomal recessive developmental delay with seizures, microcephaly, and brain atrophy, typically presenting in infancy. The gene is highly intolerant to loss-of-function variants, indicating that biallelic mutations are required for disease manifestation.

OMIM ResearchSummary from RefSeq

The protein encoded by this gene is a nucleolar protein that interacts with zinc finger 106 protein. The encoded protein has several of the same characteristics as nucleostemin and may be involved in testis development. [provided by RefSeq, Feb 2017]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.25

Clinical Summary— KNOP1

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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

60 VUS of 79 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.25LOEUF

pLI 0.000

Z-score 0.84

OE 0.77 (0.49–1.25)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.13Z-score

OE missense 0.98 (0.88–1.08)

252 obs / 257.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.77 (0.49–1.25)

0≤0.351.4

Missense OE?0.98 (0.88–1.08)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 12 / 15.6Missense obs/exp: 252 / 257.8Syn Z: 0.01

This gene — mechanism propensity

0.6260th %ile

GOF

0.5071th %ile

LOF

0.49top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

79 submitted variants in ClinVar

ClinVar

Classification Summary

VUS60

Likely Benign10

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	60	60
Likely Benign	10	10
Benign	0	0
Total	70	70

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

View in ClinVar →

15 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap KNOP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →