SLC44A4

solute carrier family 44 member 4, the group of Solute carrier family 44

Basic information

Region (hg38): 6:31863192-31879046

Previous symbols: [ "C6orf29" ]

Links

ENSG00000204385 ∙ NCBI:80736 ∙ OMIM:606107 ∙ HGNC:13941 ∙ Uniprot:Q53GD3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD
• hearing loss, autosomal dominant 72 (Limited), mode of inheritance: AD
• nonsyndromic genetic hearing loss (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal dominant, 72	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic	28013291

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC44A4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC44A4 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				26	7	33
missense			76	6	12	94
nonsense						0
start loss			1			1
frameshift			1			1
inframe indel			1	2		3
splice donor/acceptor (+/-2bp)			2	2		4
splice region			3	11	2	16
non coding			3	23	30	56
Total	0	0	84	59	49

Variants in SLC44A4

This is a list of pathogenic ClinVar variants found in the SLC44A4 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-31863656-G-A			Uncertain significance (Jan 11, 2024)
6-31863662-C-G			Uncertain significance (Jul 26, 2022)
6-31863701-T-C		not specified	Conflicting classifications of pathogenicity (Oct 23, 2023)
6-31864537-G-A			Benign (May 25, 2021)
6-31864579-CA-C			Benign (May 15, 2021)
6-31864579-C-CA			Benign (May 16, 2021)
6-31864641-G-T			Likely benign (Jan 02, 2024)
6-31864642-T-C			Likely benign (Oct 25, 2023)
6-31864668-C-T			Likely benign (Mar 20, 2023)
6-31864677-A-G			Likely benign (Nov 01, 2022)
6-31864681-A-G		not specified	Uncertain significance (Dec 07, 2023)
6-31864685-C-T			Uncertain significance (Aug 27, 2023)
6-31864686-G-A			Likely benign (Apr 20, 2023)
6-31864691-C-T			Uncertain significance (May 15, 2022)
6-31864703-C-T			Uncertain significance (May 29, 2022)
6-31864746-A-G			Uncertain significance (Dec 25, 2023)
6-31864752-C-T			Uncertain significance (Sep 02, 2021)
6-31864753-G-A			Likely benign (Oct 04, 2023)
6-31864803-G-C			Likely benign (Aug 07, 2023)
6-31864811-C-A			Likely benign (Oct 17, 2023)
6-31864837-G-A			Likely benign (Jul 19, 2023)
6-31864874-G-A		not specified	Uncertain significance (Jan 20, 2023)
6-31864876-G-A			Likely benign (May 20, 2023)
6-31864881-G-A			Uncertain significance (Jul 31, 2022)
6-31864889-A-G		not specified	Uncertain significance (Nov 07, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC44A4	protein_coding	protein_coding	ENST00000229729	21	15855

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00e-14	0.871	125483	0	265	125748	0.00105

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.11	344	407	0.845	0.0000235	4559
Missense in Polyphen		123	164.72	0.74673		1861
Synonymous	1.57	145	171	0.847	0.0000106	1419
Loss of Function	2.05	29	43.6	0.665	0.00000234	453

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00494	0.00468
Ashkenazi Jewish	0.00	0.00
East Asian	0.000328	0.000326
Finnish	0.000559	0.000554
European (Non-Finnish)	0.000863	0.000844
Middle Eastern	0.000328	0.000326
South Asian	0.00149	0.00144
Other	0.00213	0.00212

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Choline transporter that plays a role in the choline- acetylcholine system and is required to the efferent innervation of hair cells in the olivocochlear bundle for the maintenance of physiological function of outer hair cells and the protection of hair cells from acoustic injury (By similarity) (PubMed:23651124, PubMed:28013291). Also described as a thiamine pyrophosphate transporter in colon, may mediate the absorption of microbiota- generated thiamine pyrophosphate and contribute to host thiamine (vitamin B1) homeostasis (PubMed:24379411). {ECO:0000250|UniProtKB:Q7T2B0, ECO:0000269|PubMed:23651124, ECO:0000269|PubMed:24379411, ECO:0000269|PubMed:28013291}.
• Disease: DISEASE: Note=An interstitial deletion causing the fusion of exon 10 of CTL4 with the 3'-UTR of NEU has been detected in two patients affected by sialidosis.; DISEASE: Deafness, autosomal dominant, 72 (DFNA72) [MIM:617606]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA72 primarily affects the middle frequencies. It gradually progresses to whole-frequency hearing loss. {ECO:0000269|PubMed:28013291}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Choline metabolism in cancer - Homo sapiens (human);Metabolism of lipids;Amine compound SLC transporters;Metabolism;Transport of bile salts and organic acids, metal ions and amine compounds;Synthesis of PC;SLC-mediated transmembrane transport;Transport of small molecules;Glycerophospholipid biosynthesis;Phospholipid metabolism (Consensus)

Intolerance Scores

• loftool: 0.992
• rvis_EVS: 1.09
• rvis_percentile_EVS: 91.9

Haploinsufficiency Scores

• pHI: 0.394
• hipred: N
• hipred_score: 0.372
• ghis: 0.408

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.101

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc44a4

Zebrafish Information Network

• Gene name: slc44a4
• Affected structure: neuromast hair cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: phosphatidylcholine biosynthetic process;acetylcholine biosynthetic process;choline transport;positive regulation of cell growth;thiamine pyrophosphate transmembrane transport;otolith formation;neuromast hair cell development;transmembrane transport;acetylcholine secretion
• Cellular component: plasma membrane;integral component of membrane;apical plasma membrane;extracellular exosome
• Molecular function: choline transmembrane transporter activity;thiamine pyrophosphate transmembrane transporter activity