HEATR3

Chr 16AR

HEAT repeat containing 3

Also known as: DBA21, SYO1, hsSyo1

NCBI Gene: 55027ENSG00000155393UniProt: Q7Z4Q2

The protein encoded by this gene plays a role in ribosomal protein transport and in the assembly of the 5S ribonucleoprotein particle (5S RNP). The encoded protein also may be involved in NOD2-mediated NF-kappaB signaling. [provided by RefSeq, Jul 2016]

Primary Disease Associations & Inheritance

Diamond-Blackfan anemia 21MIM #620072
AR
0
Active trials
24
Pathogenic / LP
119
ClinVar variants
2
Pubs (1 yr)
1.1
Missense Z
0.82
LOEUF
Clinical Summary— HEATR3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
24 Pathogenic / Likely Pathogenic· 83 VUS of 119 total submissions
📖
GeneReview available — HEATR3
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

pubtator: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.82LOEUF
pLI 0.000
Z-score 2.28
OE 0.54 (0.36–0.82)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.14Z-score
OE missense 0.82 (0.75–0.91)
275 obs / 333.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.54 (0.36–0.82)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.75–0.91)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.02
0≤1.21.6
LoF obs/exp: 15 / 28.0Missense obs/exp: 275 / 333.4Syn Z: -0.19

ClinVar Variant Classifications

119 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic2
VUS83
Likely Benign9
Benign2
Conflicting1
22
Pathogenic
2
Likely Pathogenic
83
VUS
9
Likely Benign
2
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
3
18
0
22
Likely Pathogenic
0
1
1
0
2
VUS
0
78
5
0
83
Likely Benign
0
7
0
2
9
Benign
0
2
0
0
2
Conflicting
—1
Total191242119

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

View in ClinVar →

Protein Context — Lollipop Plot

HEATR3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients