DMXL2

Dmx like 2, the group of WD repeat domain containing

Basic information

Region (hg38): 15:51447711-51622833

Links

ENSG00000104093

∙ NCBI:23312 ∙ OMIM:612186 ∙ HGNC:2938 ∙ Uniprot:Q8TDJ6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

hearing loss, autosomal dominant 71 (Limited), mode of inheritance: AD
developmental and epileptic encephalopathy, 81 (Strong), mode of inheritance: AR
polyendocrine-polyneuropathy syndrome (Limited), mode of inheritance: AR
hearing loss, autosomal dominant 71 (Limited), mode of inheritance: AD
developmental and epileptic encephalopathy, 81 (Moderate), mode of inheritance: AR
hearing loss, autosomal dominant 71 (Limited), mode of inheritance: AD
developmental and epileptic encephalopathy, 81 (Limited), mode of inheritance: AR
genetic developmental and epileptic encephalopathy (Supportive), mode of inheritance: AD
autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD
polyendocrine-polyneuropathy syndrome (Supportive), mode of inheritance: AR
polyendocrine-polyneuropathy syndrome (Limited), mode of inheritance: Unknown
hearing loss, autosomal dominant 71 (Limited), mode of inheritance: Unknown
developmental and epileptic encephalopathy, 81 (Strong), mode of inheritance: AR
nonsyndromic genetic hearing loss (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Polyendocrine-polyneuropathy syndrome	AR	Endocrine	Among other findings, individuals may manifest with hypothyroidism, early-onset hypoglycemia, and hypogonadotropic hypogonadism, and awareness may allow medical treatment of these endocrine diosrders (for hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease)	Audiologic/Otolaryngologic; Craniofacial; Endocrine; Neurologic	25248098; 27657680; 30237576; 31688942

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DMXL2 gene.

not_provided (1513 variants)
Inborn_genetic_diseases (319 variants)
DMXL2-related_disorder (74 variants)
not_specified (29 variants)
Developmental_and_epileptic_encephalopathy,_81 (22 variants)
Hearing_loss,_autosomal_dominant_71 (18 variants)
Polyendocrine-polyneuropathy_syndrome (15 variants)
Nonsyndromic_genetic_hearing_loss (8 variants)
See_cases (3 variants)
Amenorrhea (2 variants)
Spasticity (1 variants)
Pituitary_stalk_interruption_syndrome (1 variants)
Autism_spectrum_disorder (1 variants)
Hearing_impairment (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DMXL2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001378457.1. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	492 clinvar	14 clinvar	508
missense	2 clinvar	4 clinvar	746 clinvar	38 clinvar	13 clinvar	803
nonsense	20 clinvar	1 clinvar	2 clinvar			23
start loss						0
frameshift	15 clinvar	3 clinvar	3 clinvar			21
splice donor/acceptor (+/-2bp)	1 clinvar	9 clinvar	1 clinvar			11
Total	38	17	754	530	27

Highest pathogenic variant AF is 0.00025095517

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DMXL2	protein_coding	protein_coding	ENST00000543779	43	175123

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.63e-13	125711	0	37	125748	0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.37	1297	1.56e+3	0.831	0.0000777	19905
Missense in Polyphen		521	753.04	0.69186		9636
Synonymous	-0.614	569	551	1.03	0.0000280	5813
Loss of Function	10.1	15	146	0.102	0.00000813	1800

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000209	0.000209
Ashkenazi Jewish	0.00	0.00
East Asian	0.000328	0.000326
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000118	0.000114
Middle Eastern	0.000328	0.000326
South Asian	0.000229	0.000229
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: May serve as a scaffold protein for MADD and RAB3GA on synaptic vesicles (PubMed:11809763). Plays a role in the brain as a key controller of neuronal and endocrine homeostatic processes (By similarity). {ECO:0000250|UniProtKB:Q8BPN8, ECO:0000269|PubMed:11809763}.;
Disease: DISEASE: Polyendocrine-polyneuropathy syndrome (PEPNS) [MIM:616113]: A progressive endocrine and neurodevelopmental disorder manifesting early in childhood with growth retardation and recurrent episodes of profound asymptomatic hypoglycemia. PEPNS is characterized by central hypothyroidism, hypogonadotropic hypogonadism, incomplete puberty, progressive non-autoimmune insulin-dependent diabetes mellitus, peripheral demyelinating sensorimotor polyneuropathy, and cerebellar and pyramidal signs. {ECO:0000269|PubMed:25248098}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Deafness, autosomal dominant, 71 (DFNA71) [MIM:617605]: 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. DFNA71 is characterized by bilateral mild to moderate hearing loss before age 20 years, which gradually progresses to severe to profound hearing loss. {ECO:0000269|PubMed:27657680}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.103

Intolerance Scores

loftool: 0.547
rvis_EVS: -1.88
rvis_percentile_EVS: 2

Haploinsufficiency Scores

pHI: 0.299
hipred: Y
hipred_score: 0.706
ghis: 0.540

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.606

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Dmxl2
Phenotype: homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; growth/size/body region phenotype; skeleton phenotype; immune system phenotype; 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); digestive/alimentary phenotype; neoplasm; normal 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); reproductive 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);

Zebrafish Information Network

Gene name: dmxl2
Affected structure: neuromast hair cell
Phenotype tag: abnormal
Phenotype quality: decreased acidity

Gene ontology

Biological process: vacuolar acidification
Cellular component: extracellular space;synaptic vesicle;cell junction;synaptic vesicle membrane;RAVE complex
Molecular function: Rab GTPase binding