HEATR3

protein-coding

HEAT repeat containing 3, the group of Armadillo like helical domain containing

Gene summary

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]

MANE transcript

NM_182922.4

Inheritance

ClinVar variants

P:6U:89B:11

Top phenotype

Diamond-Blackfan anemia 21

gnomAD constraint

pLI —, LoF o/e 0.54

Max pathogenic AF

—

Genomic locus

chr16:50,065,967-50,107,272

External References & Databases

Ensembl (ENSG00000155393)

Transcript & Mutation Effects

hg38 • Region Span ~41.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Diamond-Blackfan anemiaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0015253

Submitter: PanelApp Australia

Diamond-Blackfan anemia 21LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0031071

Submitter: Ambry Genetics

Diamond-Blackfan anemia 21STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0031071

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Diamond-Blackfan anemia 21AR

Manifestation: Cardiovascular; Craniofacial; Hematologic; Musculoskeletal; Neurologic; Oncologic

Intervention: Cardiovascular; Hematologic; Oncologic

Rationale: The condition can include congenital cardiac anomalies, and awareness may allow early diagnosis and management; The condition may involve severe anemia, and interventions such as transfusions have been described; Individuals may be at an increased risk of certain types of cancer, and awareness may allow early diagnosis and management of oncologic manifestations

Refs: 35213692

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HEATR3 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 80

Diamond-Blackfan anemia 21Total: 12

not providedTotal: 7

Diamond-Blackfan anemia 1Total: 3

Diamond-Blackfan anemiaTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_182922.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	2 clinvar		3
missense	2 clinvar	1 clinvar	87 clinvar	7 clinvar	2 clinvar	99
nonsense		2 clinvar	1 clinvar			3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)	1 clinvar					1
Total	3	3	89	9	2	106

Highest pathogenic variant AF is 0.0000012393324

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_182922.4	RefSeq	NP_891552.1	15	MANE Select
ENST00000299192.8	Ensembl	ENSP00000299192.7	15	MANE Select
NM_001329729.2	RefSeq	NP_001316658.1	13	Standard
NM_001329730.2	RefSeq	NP_001316659.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein import into nucleus
ribosomal large subunit biogenesis

Molecular Function

unfolded protein binding

Cellular Component

cell

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000299192
Coding exons: 15
Length: 40447
Individuals with no LoFs: 125701
Homozygous LoFs: 0
Heterozygous LoFs: 46
Defined: 125747
p: 0.000183

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.14	275	333	0.825	0.0000160	4429
Missense (PolyPhen)		37	64.493	0.57371		901
Synonymous	-0.187	131	128	1.02	0.00000692	1320
Loss of Function	2.28	15	28.0	0.536	0.00000118	389

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00030	0.00029	rare
Ashkenazi Jewish	0.00020	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.00018	0.00018	rare
South Asian	0.00016	0.00016	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.752
RVIS EVS: 0.11
RVIS percentile EVS: 62

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: N
Indispensability score: 0.387

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium