NHLH2

nescient helix-loop-helix 2, the group of Basic helix-loop-helix proteins

Basic information

Region (hg38): 1:115836377-115843917

Previous symbols: [ "HEN2" ]

Links

ENSG00000177551 ∙ NCBI:4808 ∙ OMIM:162361 ∙ HGNC:7818 ∙ Uniprot:Q02577 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 4 of 8.

Transcript ID	Protein ID	Coding exons	MANE Select	MANE Plus Clinical
NM_005599.3	NP_005590.1	1	yes	-
ENST00000320238.3	ENSP00000322087.3	1	yes	-
NM_001111061.2	NP_001104531.1	1	-	-
ENST00000429731.1	ENSP00000405062.1	1	-	-

Phenotypes

GenCC

Source: genCC

• hypogonadotropic hypogonadism 27 without anosmia (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypogonadotropic hypogonadism 27 without anosmia	AR	Endocrine	In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease	Endocrine	35066646

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NHLH2 gene.

• not_specified (11 variants)
• Hypogonadotropic_hypogonadism (4 variants)
• Hypogonadotropic_hypogonadism_27_without_anosmia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NHLH2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_005599.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			15			15
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	15	0	0

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NHLH2	protein_coding	protein_coding	ENST00000369506	1	7541

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.05	50	75.6	0.661	0.00000350	840
Missense in Polyphen		9	32.644	0.2757		352
Synonymous	-1.04	43	35.1	1.22	0.00000169	285
Loss of Function	1.52	0	2.68	0.00	1.18e-7	33

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
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	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May serve as DNA-binding protein and may be involved in the control of cell-type determination, possibly within the developing nervous system.
• Pathway: Prader-Willi and Angelman Syndrome (Consensus)

Recessive Scores

• pRec: 0.136

Intolerance Scores

• rvis_EVS: 0.12
• rvis_percentile_EVS: 62.38

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.307

Gene Damage Prediction

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

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II;central nervous system development;mating behavior;cell differentiation;ovulation cycle;positive regulation of transcription by RNA polymerase II;positive regulation of DNA-binding transcription factor activity
• Cellular component: nucleus;transcription factor complex
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;RNA polymerase II activating transcription factor binding;DNA-binding transcription activator activity, RNA polymerase II-specific;protein binding;protein dimerization activity