MAMLD1

mastermind like domain containing 1

Basic information

Region (hg38): X:150361422-150514178

Previous symbols: [ "CXorf6" ]

Links

ENSG00000013619

∙ NCBI:10046 ∙ OMIM:300120 ∙ HGNC:2568 ∙ Uniprot:Q13495 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

hypospadias 2, X-linked (Strong), mode of inheritance: XL
hypospadias 2, X-linked (Strong), mode of inheritance: XL
hypospadias 2, X-linked (Strong), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypospadias 2, X-linked	XL	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	Genitourinary	17086185

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MAMLD1 gene.

Inborn_genetic_diseases (64 variants)
not_provided (63 variants)
Hypospadias_2,_X-linked (13 variants)
MAMLD1-related_disorder (11 variants)
not_specified (7 variants)
Disorder_of_sexual_differentiation (1 variants)
46,XY_ovotesticular_disorder_of_sex_development (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAMLD1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005491.5. 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			1 clinvar	12 clinvar	13 clinvar	26
missense			70 clinvar	12 clinvar	9 clinvar	91
nonsense	5 clinvar					5
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)						0
Total	6	0	71	24	22

Highest pathogenic variant AF is 9.10578e-7

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAMLD1	protein_coding	protein_coding	ENST00000432680	4	152760

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.626	0.373	124588	1	0	124589	0.00000401

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.599	330	362	0.911	0.0000275	6497
Missense in Polyphen		94	109.08	0.86175		2075
Synonymous	-0.896	165	151	1.09	0.0000127	2108
Loss of Function	3.39	4	20.6	0.194	0.00000155	318

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)	0.0000124	0.00000894
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Transactivates the HES3 promoter independently of NOTCH proteins. HES3 is a non-canonical NOTCH target gene which lacks binding sites for RBPJ. {ECO:0000269|PubMed:18162467}.;
Disease: DISEASE: Hypospadias 2, X-linked (HYSP2) [MIM:300758]: A common malformation in which the urethra opens on the ventral side of the penis, due to developmental arrest of urethral fusion. The opening can be located glandular, penile, or even more posterior in the scrotum or perineum. Hypospadias is a feature of several syndromic disorders, including the androgen insensitivity syndrome and Opitz syndrome. {ECO:0000269|PubMed:17086185}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Disease;RUNX3 regulates NOTCH signaling;Signal Transduction;Gene expression (Transcription);Transcriptional regulation by RUNX3;Generic Transcription Pathway;RNA Polymerase II Transcription;Notch-HLH transcription pathway;NICD traffics to nucleus;Pre-NOTCH Transcription and Translation;Pre-NOTCH Expression and Processing;Signaling by NOTCH1;NOTCH2 intracellular domain regulates transcription;Signaling by NOTCH2;NOTCH3 Intracellular Domain Regulates Transcription;Signaling by NOTCH3;Signaling by NOTCH;Constitutive Signaling by NOTCH1 PEST Domain Mutants;Signaling by NOTCH1 PEST Domain Mutants in Cancer;Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants;Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer;Signaling by NOTCH1 in Cancer;Diseases of signal transduction;NOTCH1 Intracellular Domain Regulates Transcription (Consensus)

Recessive Scores

pRec: 0.145

Haploinsufficiency Scores

pHI: 0.711
hipred: N
hipred_score: 0.325
ghis: 0.491

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.0709

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Mamld1
Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; skeleton phenotype; immune system phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype;

Gene ontology

Biological process: male gonad development
Cellular component: cellular_component;nucleoplasm;Golgi apparatus;centrosome;nuclear body
Molecular function: molecular_function