HAND1

heart and neural crest derivatives expressed 1, the group of Basic helix-loop-helix proteins

Basic information

Region (hg38): 5:154474971-154478227

Links

ENSG00000113196 ∙ NCBI:9421 ∙ OMIM:602406 ∙ HGNC:4807 ∙ Uniprot:O96004 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital heart disease (Moderate), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HAND1 gene.

• Hypoplastic left heart syndrome (94 variants)
• not provided (8 variants)
• Inborn genetic diseases (7 variants)
• not specified (3 variants)
• HAND1-related condition (2 variants)
• Hypoplastic left heart syndrome 1 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HAND1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	30	3	34
missense			52	5	1	58
nonsense			1			1
start loss			1			1
frameshift			1			1
inframe indel			2			2
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1	1	3	5
Total	0	0	59	36	7

Variants in HAND1

This is a list of pathogenic ClinVar variants found in the HAND1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-154475807-C-T		Hypoplastic left heart syndrome	Uncertain significance (May 08, 2022)
5-154475814-T-G		Hypoplastic left heart syndrome	Uncertain significance (Aug 17, 2023)
5-154475839-C-A		Hypoplastic left heart syndrome	Likely benign (Oct 13, 2023)
5-154475839-C-G		Hypoplastic left heart syndrome	Likely benign (Oct 04, 2023)
5-154475845-G-C		Hypoplastic left heart syndrome	Likely benign (Nov 27, 2023)
5-154475846-C-G		HAND1-related disorder • Hypoplastic left heart syndrome	Uncertain significance (Nov 07, 2023)
5-154475848-G-A		Hypoplastic left heart syndrome	Likely benign (Oct 18, 2022)
5-154475850-T-C		Hypoplastic left heart syndrome	Uncertain significance (Mar 22, 2022)
5-154475854-T-C		Hypoplastic left heart syndrome	Likely benign (Aug 18, 2022)
5-154475854-T-G		Hypoplastic left heart syndrome	Likely benign (Dec 03, 2021)
5-154475867-T-C		Hypoplastic left heart syndrome	Uncertain significance (Nov 14, 2022)
5-154475873-A-G		not specified	Uncertain significance (Jan 07, 2022)
5-154475875-T-G		Hypoplastic left heart syndrome	Likely benign (Apr 11, 2023)
5-154475880-C-T		Hypoplastic left heart syndrome	Uncertain significance (Oct 12, 2021)
5-154475888-G-A		Hypoplastic left heart syndrome	Uncertain significance (Nov 08, 2023)
5-154475889-G-A		Hypoplastic left heart syndrome	Uncertain significance (Feb 06, 2022)
5-154475890-A-G		Hypoplastic left heart syndrome	Likely benign (Jul 07, 2023)
5-154475892-G-C		not specified	Uncertain significance (Feb 23, 2023)
5-154475903-T-A		Hypoplastic left heart syndrome	Uncertain significance (Jul 19, 2022)
5-154475903-T-C		not specified	Uncertain significance (Oct 10, 2023)
5-154475923-A-C		Hypoplastic left heart syndrome	Likely benign (Mar 22, 2023)
5-154475928-G-C		Hypoplastic left heart syndrome	Likely benign (Nov 27, 2023)
5-154477396-T-C			Benign (May 26, 2021)
5-154477414-C-G			Benign (May 12, 2021)
5-154477447-T-A		Hypoplastic left heart syndrome	Likely benign (Jan 03, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HAND1	protein_coding	protein_coding	ENST00000231121	2	3293

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.109	0.786	125691	0	3	125694	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.284	133	124	1.07	0.00000587	1377
Missense in Polyphen		34	36.396	0.93416		428
Synonymous	-1.18	64	53.1	1.21	0.00000271	449
Loss of Function	1.27	2	5.09	0.393	2.19e-7	66

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000904	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription factor that plays an essential role in both trophoblast-giant cells differentiation and in cardiac morphogenesis. In the adult, could be required for ongoing expression of cardiac-specific genes. Binds the DNA sequence 5'- NRTCTG-3' (non-canonical E-box) (By similarity). {ECO:0000250}.
• Pathway: Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);Heart Development;Neural Crest Differentiation;Mesodermal Commitment Pathway;nfat and hypertrophy of the heart (Consensus)

Recessive Scores

• pRec: 0.230

Intolerance Scores

• loftool: 0.216
• rvis_EVS: 0.04
• rvis_percentile_EVS: 56.64

Haploinsufficiency Scores

• pHI: 0.325
• hipred: Y
• hipred_score: 0.516
• ghis: 0.458

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.994

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hand1
• Phenotype: respiratory system phenotype; embryo phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); reproductive system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); digestive/alimentary phenotype; limbs/digits/tail phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; craniofacial phenotype; muscle phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;angiogenesis;mesoderm formation;blastocyst development;trophectodermal cell differentiation;heart looping;embryonic heart tube formation;cardiac left ventricle formation;cardiac right ventricle formation;transcription by RNA polymerase II;heart development;embryonic heart tube development;odontogenesis of dentin-containing tooth;negative regulation of DNA-binding transcription factor activity;negative regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;ventricular cardiac muscle tissue morphogenesis;cardiac septum morphogenesis;mesenchyme development;cartilage morphogenesis;trophoblast giant cell differentiation;negative regulation of RNA polymerase II regulatory region sequence-specific DNA binding
• Cellular component: nucleus;nucleoplasm;nucleolus;cytoplasm;RNA polymerase II transcription factor complex
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;transcription coactivator activity;protein binding;transcription factor binding;enzyme binding;identical protein binding;protein homodimerization activity;bHLH transcription factor binding;transcription regulatory region DNA binding;protein heterodimerization activity