FHL2

four and a half LIM domains 2, the group of LIM domain containing

Basic information

Region (hg38): 2:105357712-105438513

Links

ENSG00000115641 ∙ NCBI:2274 ∙ OMIM:602633 ∙ HGNC:3703 ∙ Uniprot:Q14192 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FHL2 gene.

• Primary_dilated_cardiomyopathy (204 variants)
• not_specified (62 variants)
• Cardiomyopathy (15 variants)
• FHL2-related_disorder (12 variants)
• not_provided (11 variants)
• Primary_familial_hypertrophic_cardiomyopathy (1 variants)
• Left_ventricular_noncompaction_cardiomyopathy (1 variants)
• Arrhythmogenic_right_ventricular_cardiomyopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FHL2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001318895.3. 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			1	45	4	50
missense			130	6	1	137
nonsense			4			4
start loss			2			2
frameshift			5			5
splice donor/acceptor (+/-2bp)			3			3
Total	0	0	145	51	5

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FHL2	protein_coding	protein_coding	ENST00000358129	5	80802

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000287	0.794	125729	0	18	125747	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.899	137	170	0.806	0.00000999	1873
Missense in Polyphen		59	76.1	0.77529		843
Synonymous	0.309	59	62.1	0.950	0.00000360	466
Loss of Function	1.22	9	13.9	0.648	5.88e-7	178

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000120	0.000120
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000106	0.000105
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.000167	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May function as a molecular transmitter linking various signaling pathways to transcriptional regulation. Negatively regulates the transcriptional repressor E4F1 and may function in cell growth. Inhibits the transcriptional activity of FOXO1 and its apoptotic function by enhancing the interaction of FOXO1 with SIRT1 and FOXO1 deacetylation. Negatively regulates the calcineurin/NFAT signaling pathway in cardiomyocytes (PubMed:28717008). {ECO:0000269|PubMed:15692560, ECO:0000269|PubMed:16652157, ECO:0000269|PubMed:18853468, ECO:0000269|PubMed:28717008}.
• Pathway: Osteoclast differentiation - Homo sapiens (human);Androgen receptor signaling pathway;RANKL-RANK (Receptor activator of NFKB (ligand)) Signaling Pathway;Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha);Ectoderm Differentiation;VEGFA-VEGFR2 Signaling Pathway;hypoxia and p53 in the cardiovascular system;AndrogenReceptor;Coregulation of Androgen receptor activity;ID;Signaling events mediated by HDAC Class III (Consensus)

Recessive Scores

• pRec: 0.435

Intolerance Scores

• loftool: 0.0595
• rvis_EVS: 0.31
• rvis_percentile_EVS: 72.23

Haploinsufficiency Scores

• pHI: 0.436
• hipred: Y
• hipred_score: 0.738
• ghis: 0.399

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.930

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fhl2
• Phenotype: skeleton 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); normal phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;osteoblast differentiation;response to hormone;regulation of lipid metabolic process;androgen receptor signaling pathway;negative regulation of apoptotic process;positive regulation of transcription, DNA-templated;atrial cardiac muscle cell development;ventricular cardiac muscle cell development;heart trabecula formation;negative regulation of calcineurin-NFAT signaling cascade
• Cellular component: nucleus;nucleoplasm;focal adhesion;Z disc;M band
• Molecular function: transcription coactivator activity;protein binding;transcription factor binding;identical protein binding;metal ion binding;androgen receptor binding