MARVELD2

MARVEL domain containing 2, the group of MARVEL domain containing

Basic information

Region (hg38): 5:69415065-69444330

Previous symbols: [ "MRVLDC2", "DFNB49" ]

Links

ENSG00000152939 ∙ NCBI:153562 ∙ OMIM:610572 ∙ HGNC:26401 ∙ Uniprot:Q8N4S9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive nonsyndromic hearing loss 49 (Moderate), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Definitive), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 49 (Strong), mode of inheritance: AR
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 49 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 49	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	15538632; 17186462; 18084694

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MARVELD2 gene.

• not_provided (151 variants)
• Autosomal_recessive_nonsyndromic_hearing_loss_49 (66 variants)
• Inborn_genetic_diseases (55 variants)
• not_specified (37 variants)
• MARVELD2-related_disorder (8 variants)
• Hearing_loss,_autosomal_recessive (4 variants)
• Rare_genetic_deafness (3 variants)
• Hearing_impairment (2 variants)
• Deafness (1 variants)
• Ehlers-Danlos_syndrome,_spondylodysplastic_type,_2 (1 variants)
• See_cases (1 variants)
• Monogenic_hearing_loss (1 variants)
• Ear_malformation (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MARVELD2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001038603.3. 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			4	50	1	55
missense		1	112	14		127
nonsense	8	8				16
start loss						0
frameshift	9	10				19
splice donor/acceptor (+/-2bp)	2	3				5
Total	19	22	116	64	1

Highest pathogenic variant AF is 0.00027036414

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MARVELD2	protein_coding	protein_coding	ENST00000325631	6	29219

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125613	0	135	125748	0.000537

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.197	308	318	0.969	0.0000183	3641
Missense in Polyphen		110	116.93	0.94077		1377
Synonymous	0.306	118	122	0.965	0.00000742	1092
Loss of Function	0.846	21	25.6	0.820	0.00000162	299

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000565	0.000564
Ashkenazi Jewish	0.00	0.00
East Asian	0.000544	0.000544
Finnish	0.000370	0.000370
European (Non-Finnish)	0.000643	0.000642
Middle Eastern	0.000544	0.000544
South Asian	0.000849	0.000850
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in the formation of tricellular tight junctions and of epithelial barriers (By similarity). Required for normal hearing via its role in the separation of the endolymphatic and perilymphatic spaces of the organ of Corti in the inner ear, and for normal survival of hair cells in the organ of Corti (PubMed:17186462). {ECO:0000250|UniProtKB:Q3UZP0, ECO:0000269|PubMed:17186462}.
• Disease: DISEASE: Deafness, autosomal recessive, 49 (DFNB49) [MIM:610153]: 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. {ECO:0000269|PubMed:17186462}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Tight junction - Homo sapiens (human);EGFR1 (Consensus)

Recessive Scores

• pRec: 0.105

Intolerance Scores

• loftool: 0.959
• rvis_EVS: -0.35
• rvis_percentile_EVS: 29.43

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.249

Gene Damage Prediction

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

Gene ontology

• Biological process: sensory perception of sound;cell-cell junction organization;establishment of endothelial barrier;bicellular tight junction assembly
• Cellular component: cytoplasm;bicellular tight junction;integral component of membrane;basolateral plasma membrane;apical plasma membrane;cell junction;cytoplasmic vesicle;paranodal junction;Schmidt-Lanterman incisure;tricellular tight junction
• Molecular function: protein binding