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: XLR
• 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.

• Hypospadias 2, X-linked (2 variants)
• not provided (2 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.

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			1	11	8	20
missense			26	8	11	45
nonsense	3					3
start loss						0
frameshift	1					1
inframe indel			1	4		5
splice donor/acceptor (+/-2bp)						0
splice region				2		2
non coding			3	5	2	10
Total	4	0	31	28	21

Variants in MAMLD1

This is a list of pathogenic ClinVar variants found in the MAMLD1 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-150445536-G-A		Disorder of sexual differentiation	Uncertain significance (Sep 01, 2021)
X-150445573-G-A		Inborn genetic diseases	Uncertain significance (Sep 27, 2022)
X-150445631-G-C			Likely benign (Aug 16, 2022)
X-150462791-T-C			Uncertain significance (Jul 01, 2024)
X-150462831-A-G			Benign (Nov 25, 2023)
X-150462853-A-T		MAMLD1-related disorder	Likely benign (Feb 04, 2020)
X-150462856-A-T		MAMLD1-related disorder	Likely benign (Feb 04, 2020)
X-150469782-A-G			Benign (Mar 10, 2022)
X-150469795-G-A		Inborn genetic diseases	Uncertain significance (Jun 17, 2024)
X-150469843-T-A			Uncertain significance (Nov 21, 2022)
X-150469843-T-C			Benign/Likely benign (Dec 15, 2023)
X-150469875-C-T			Likely benign (Apr 14, 2023)
X-150469934-G-A			Likely benign (-)
X-150469967-G-T		Hypospadias 2, X-linked	Pathogenic (Jul 31, 2017)
X-150469979-A-T		Inborn genetic diseases	Uncertain significance (Mar 20, 2023)
X-150470001-C-T		Inborn genetic diseases	Uncertain significance (Mar 15, 2024)
X-150470024-A-G		Inborn genetic diseases	Likely benign (Jan 23, 2023)
X-150470034-G-T		Inborn genetic diseases	Uncertain significance (Nov 03, 2023)
X-150470078-G-A			Likely benign (Jan 17, 2023)
X-150470082-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 23, 2024)
X-150470149-T-A			Uncertain significance (May 04, 2021)
X-150470162-G-T		Hypospadias 2, X-linked	Pathogenic (Dec 01, 2006)
X-150470178-C-T		not specified	Benign (Jan 02, 2024)
X-150470179-G-A			Benign (Oct 03, 2023)
X-150470381-C-T		Hypospadias 2, X-linked	Pathogenic (Dec 01, 2006)

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