FLVCR2

FLVCR heme transporter 2, the group of MicroRNA protein coding host genes|Solute carrier family 49

Basic information

Region (hg38): 14:75578619-75663214

Previous symbols: [ "C14orf58" ]

Links

ENSG00000119686 ∙ NCBI:55640 ∙ OMIM:610865 ∙ HGNC:20105 ∙ Uniprot:Q9UPI3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Fowler syndrome (Definitive), mode of inheritance: AR
• Fowler syndrome (Strong), mode of inheritance: AR
• Fowler syndrome (Moderate), mode of inheritance: AR
• Fowler syndrome (Strong), mode of inheritance: AR
• Fowler syndrome (Supportive), mode of inheritance: AR
• Fowler syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Proliferative vasculopathy and hydraencephaly-hydrocephaly syndrome	AR	General	Treatment may involve dietary modification (eg, to restrict trimethylamine precursors), and medical/dietary treatment (eg, with agents such as metronidazole, neomycin, lactulose, copper chlorphyllin, activated charcoal, (E, E)-2, 4-undecadienal) as well as riboflavin supplementation (the use of specific pH soaps may be beneficial as well)	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic	7474897; 9398858; 9846928; 10646019; 10485731; 12653714; 12893987; 12938085; 15565078; 16601883; 20301282; 22126753; 23430514

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FLVCR2 gene.

• not provided (94 variants)
• Posterior column ataxia-retinitis pigmentosa syndrome (63 variants)
• Inborn genetic diseases (18 variants)
• Fowler syndrome (14 variants)
• not specified (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FLVCR2 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			4	12	4	20
missense			48	5	2	55
nonsense			1			1
start loss						0
frameshift	1	2	1			4
inframe indel			2	1		3
splice donor/acceptor (+/-2bp)						0
splice region			1	1		2
non coding			27	22	24	73
Total	1	2	83	40	30

Highest pathogenic variant AF is 0.0000131

Variants in FLVCR2

This is a list of pathogenic ClinVar variants found in the FLVCR2 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-75578850-GTC-G		Fowler syndrome	Benign (Nov 26, 2021)
14-75578862-T-C		Posterior column ataxia-retinitis pigmentosa syndrome	Benign/Likely benign (Dec 13, 2019)
14-75578877-T-C		Posterior column ataxia-retinitis pigmentosa syndrome	Benign (Nov 11, 2018)
14-75578902-C-T		Posterior column ataxia-retinitis pigmentosa syndrome	Benign (Nov 23, 2019)
14-75578980-A-G		Inborn genetic diseases	Uncertain significance (Oct 01, 2022)
14-75579019-T-C		not specified • Posterior column ataxia-retinitis pigmentosa syndrome • Fowler syndrome	Benign (Jan 29, 2024)
14-75579022-C-CG			Pathogenic (Sep 14, 2023)
14-75579023-G-A			Likely benign (Nov 27, 2023)
14-75579041-G-A		Posterior column ataxia-retinitis pigmentosa syndrome	Uncertain significance (Jan 13, 2018)
14-75579044-CCCCAGCGTCTCGGTCCAT-C			Likely benign (Jan 29, 2024)
14-75579050-C-A		Posterior column ataxia-retinitis pigmentosa syndrome	Uncertain significance (Jan 13, 2018)
14-75579051-G-A			Uncertain significance (Jun 13, 2022)
14-75579075-G-A		Inborn genetic diseases	Conflicting classifications of pathogenicity (May 06, 2022)
14-75579107-C-T			Likely benign (May 02, 2018)
14-75579128-G-T			Likely benign (Jun 07, 2022)
14-75579136-C-T		Posterior column ataxia-retinitis pigmentosa syndrome • Inborn genetic diseases	Uncertain significance (Dec 27, 2023)
14-75579149-CCAACCCAGTGGCTTGGCT-C			Uncertain significance (Oct 19, 2022)
14-75579216-A-T			Uncertain significance (Aug 07, 2023)
14-75579223-G-A			Uncertain significance (Aug 13, 2022)
14-75579239-G-A			Likely benign (May 19, 2022)
14-75579249-T-C		Posterior column ataxia-retinitis pigmentosa syndrome	Uncertain significance (Jan 13, 2018)
14-75579258-A-G		Posterior column ataxia-retinitis pigmentosa syndrome	Conflicting classifications of pathogenicity (Oct 03, 2023)
14-75579262-G-A		Inborn genetic diseases	Uncertain significance (Jul 19, 2022)
14-75579281-C-T			Likely benign (Oct 13, 2023)
14-75579294-A-G			Uncertain significance (Aug 19, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FLVCR2	protein_coding	protein_coding	ENST00000238667	10	84598

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000343	0.945	125702	0	46	125748	0.000183

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0642	293	296	0.990	0.0000175	3425
Missense in Polyphen		83	82.298	1.0085		1003
Synonymous	-0.0521	122	121	1.01	0.00000803	1097
Loss of Function	1.82	12	21.0	0.572	0.00000102	244

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000445	0.000445
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000109	0.000109
Finnish	0.000185	0.000139
European (Non-Finnish)	0.000185	0.000185
Middle Eastern	0.000109	0.000109
South Asian	0.000229	0.000229
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as an importer of heme. Also acts as a transporter for a calcium-chelator complex, important for growth and calcium metabolism. {ECO:0000269|PubMed:20823265}.

Recessive Scores

• pRec: 0.147

Intolerance Scores

• loftool: 0.633
• rvis_EVS: 0.35
• rvis_percentile_EVS: 74.49

Haploinsufficiency Scores

• pHI: 0.234
• hipred: N
• hipred_score: 0.289
• ghis: 0.453

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.113

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Flvcr2
• Phenotype: immune system phenotype; embryo phenotype; respiratory system 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); neoplasm; 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)

Gene ontology

• Biological process: transmembrane transport;heme export
• Cellular component: plasma membrane;integral component of membrane
• Molecular function: heme transporter activity;heme binding