CFC1

cripto, FRL-1, cryptic family 1

Basic information

Region (hg38): 2:130592165-130599575

Previous symbols: [ "HTX2" ]

Links

ENSG00000136698 ∙ NCBI:55997 ∙ OMIM:605194 ∙ HGNC:18292 ∙ Uniprot:P0CG37 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• heterotaxy, visceral, 2, autosomal (Strong), mode of inheritance: AD
• heterotaxy, visceral, 2, autosomal (Strong), mode of inheritance: AD
• heterotaxy, visceral, 2, autosomal (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Heterotaxy, visceral, 2, autosomal dominant	AD	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Gastrointestinal	11062482; 11562933; 11799476; 18538293

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CFC1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CFC1 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		6	7
missense			6	3	4	13
nonsense						0
start loss						0
frameshift			2			2
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	10	3	10

Variants in CFC1

This is a list of pathogenic ClinVar variants found in the CFC1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-130592934-G-C		not specified	Benign (May 11, 2014)
2-130592943-C-G		not specified	Benign (Jan 16, 2013)
2-130592949-C-A		not specified	Benign (Feb 27, 2014)
2-130592953-G-A			Uncertain significance (Feb 21, 2024)
2-130592961-G-T		not specified	Benign (Jan 16, 2013)
2-130592965-G-A		Inborn genetic diseases	Uncertain significance (Oct 05, 2021)
2-130593026-C-T			Benign (Oct 01, 2024)
2-130593026-CG-C		Heterotaxy, visceral, 2, autosomal • not specified	Conflicting classifications of pathogenicity (Mar 29, 2024)
2-130593065-A-G		Heterotaxy, visceral, 2, autosomal	Benign (May 28, 2019)
2-130597533-C-T		not specified • Heterotaxy, visceral, 2, autosomal	Benign (May 28, 2019)
2-130597849-C-CGCGCACCCCTGTGCCCACCT		Heterotaxy, visceral, 2, autosomal	Pathogenic (Mar 01, 2002)
2-130597896-G-A		Heterotaxy, visceral, 2, autosomal	Pathogenic (Nov 01, 2000)
2-130597899-C-T			Uncertain significance (Dec 01, 2023)
2-130597962-AGCGCGGCC-A			Uncertain significance (Jul 13, 2022)
2-130598654-C-T		Inborn genetic diseases	Uncertain significance (Jan 02, 2024)
2-130598657-G-A			Likely benign (Mar 03, 2015)
2-130598664-G-T		not specified	Benign (Nov 04, 2013)
2-130598675-C-T		Inborn genetic diseases	Uncertain significance (Apr 06, 2022)
2-130598678-C-G		Inborn genetic diseases	Likely benign (Oct 25, 2022)
2-130598680-G-A		Inborn genetic diseases	Uncertain significance (Aug 16, 2021)
2-130598681-G-GCCCCCAGCCCTC		not specified	Uncertain significance (Feb 01, 2023)
2-130598685-C-A			Uncertain significance (Feb 06, 2016)
2-130598714-C-T		Inborn genetic diseases	Likely benign (May 30, 2023)
2-130598749-C-T		not specified	Benign (Aug 07, 2013)
2-130598792-C-T		Inborn genetic diseases	Uncertain significance (Jun 30, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CFC1	protein_coding	protein_coding	ENST00000259216	6	6785

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.105	0.785	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.224	43	39.1	1.10	0.00000211	1370
Missense in Polyphen		2	2.3308	0.85806		358
Synonymous	-0.837	25	20.2	1.24	0.00000148	447
Loss of Function	1.24	2	4.99	0.401	2.64e-7	114

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: NODAL coreceptor involved in the correct establishment of the left-right axis. May play a role in mesoderm and/or neural patterning during gastrulation. {ECO:0000269|PubMed:11062482}.
• Disease: DISEASE: Heterotaxy, visceral, 2, autosomal (HTX2) [MIM:605376]: A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. Visceral heterotaxy or situs ambiguus results in randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left-right axis and with respect to one another. It can been associated with variety of congenital defects including cardiac malformations. {ECO:0000269|PubMed:11062482, ECO:0000269|PubMed:11799476}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Developmental Biology;Regulation of signaling by NODAL;Signaling by NODAL (Consensus)

Recessive Scores

• pRec: 0.128

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.255
• ghis: 0.506

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.147

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cfc1
• Phenotype: digestive/alimentary phenotype; immune system phenotype; liver/biliary system phenotype; respiratory system phenotype; embryo 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); growth/size/body region 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); hematopoietic system phenotype

Gene ontology

• Biological process: determination of left/right symmetry;gastrulation;heart development;anterior/posterior pattern specification;BMP signaling pathway;nodal signaling pathway;anatomical structure development
• Cellular component: cellular_component;extracellular region;plasma membrane;cell surface;anchored component of membrane
• Molecular function: molecular_function;signaling receptor binding;nodal binding;activin receptor binding