POU5F1B

Chr 8

POU class 5 homeobox 1B

Also known as: OCT4-PG1, OCT4PG1, OTF3C, OTF3P1, POU5F1P1, POU5F1P4, POU5FLC20, POU5FLC8

NCBI Gene: 5462 ENSG00000212993 UniProt: Q06416 OMIM: 615739

POU5F1B encodes a transcription factor with weak transcriptional activator activity that may function in eye development. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly and simplified gyral pattern, typically presenting in infancy. The gene is not highly constrained against loss-of-function variants, which is consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

This intronless gene was thought to be a transcribed pseudogene of POU class 5 homeobox 1, however, it has been reported that this gene can encode a functional protein. The encoded protein is nearly the same length as and highly similar to the POU class 5 homeobox 1 transcription factor, has been shown to be a weak transcriptional activator and may play a role in carcinogenesis and eye development. [provided by RefSeq, Apr 2009]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.85

Clinical Summary— POU5F1B

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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

57 VUS of 58 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?

1.85LOEUF

pLI 0.000

Z-score -0.19

OE 1.10 (0.56–1.85)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.36Z-score

OE missense 1.07 (0.96–1.20)

205 obs / 191.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.10 (0.56–1.85)

0≤0.351.4

Missense OE?1.07 (0.96–1.20)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 5 / 4.6Missense obs/exp: 205 / 191.2Syn Z: -0.88

This gene — mechanism propensity

0.6552th %ile

GOF

0.4677th %ile

LOF

0.54top 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

58 submitted variants in ClinVar

ClinVar

Classification Summary

VUS57

Likely Benign1

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	57	0	57
Likely Benign	0	1	1
Benign	0	0	0
Total	57	1	58

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

View in ClinVar →

55 pathogenic / likely-pathogenic (of 55) ClinVar copy-number / structural variants overlap POU5F1B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →