SP3

Chr 2

Sp3 transcription factor

Also known as: SPR2

NCBI Gene: 6670 ENSG00000172845 UniProt: Q02447 OMIM: 601804

This gene belongs to a family of Sp1 related genes that encode transcription factors that regulate transcription by binding to consensus GC- and GT-box regulatory elements in target genes. This protein contains a zinc finger DNA-binding domain and several transactivation domains, and has been reported to function as a bifunctional transcription factor that either stimulates or represses the transcription of numerous genes. Transcript variants encoding different isoforms have been described for this gene, and one has been reported to initiate translation from a non-AUG (AUA) start codon. Additional isoforms, resulting from the use of alternate downstream translation initiation sites, have also been noted. A related pseudogene has been identified on chromosome 13. [provided by RefSeq, Feb 2010]

OMIM Research

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.15

Clinical Summary— SP3

⚡

Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

📋

ClinVar Variants

96 VUS of 114 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.15LOEUF

pLI 1.000

Z-score 5.11

OE 0.03 (0.01–0.15)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

1.63Z-score

OE missense 0.77 (0.70–0.85)

309 obs / 400.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.03 (0.01–0.15)

0≤0.351.4

Missense OE?0.77 (0.70–0.85)

0≤0.61.4

Synonymous OE?1.29

0≤1.21.6

LoF obs/exp: 1 / 32.4Missense obs/exp: 309 / 400.8Syn Z: -2.82

This gene — mechanism propensity

0.3495th %ile

GOF

0.16100th %ile

LOF

0.83top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.15

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

114 submitted variants in ClinVar

ClinVar

Classification Summary

VUS96

Likely Benign1

Benign4

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	1	95	0	96
Likely Benign	0	1	0	1
Benign	0	1	3	4
Total	1	97	3	101

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

View in ClinVar →

27 pathogenic / likely-pathogenic (of 34) ClinVar copy-number / structural variants overlap SP3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →