MAMLD1 (mastermind like domain containing 1)

Gene

• Entrez ID: 10046
• Gene name: Mastermind like domain containing 1
• Gene symbol: MAMLD1
• Synonyms (NCBI Gene): CG1, CXorf6, F18, HYSP2
• Chromosome: X
• Chromosome location: Xq28
• Summary: This gene encodes a mastermind-like domain containing protein. This protein may function as a transcriptional co-activator. Mutations in this gene are the cause of X-linked hypospadias type 2. Alternate splicing results in multiple transcript variants. [p

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121909493	G>T	Pathogenic	Coding sequence variant, stop gained
rs121909494	C>T	Pathogenic	Coding sequence variant, stop gained
rs121909495	C>T	Pathogenic	Coding sequence variant, stop gained, intron variant
rs1135402752	G>T	Pathogenic	Coding sequence variant, stop gained

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017096	hsa-miR-335-5p	Microarray	18185580
MIRT456091	hsa-miR-6758-5p	PAR-CLIP	23592263
MIRT456092	hsa-miR-6856-5p	PAR-CLIP	23592263
MIRT456090	hsa-miR-6873-5p	PAR-CLIP	23592263
MIRT456089	hsa-miR-3927-3p	PAR-CLIP	23592263
MIRT456088	hsa-miR-6831-5p	PAR-CLIP	23592263
MIRT456087	hsa-miR-4451	PAR-CLIP	23592263
MIRT456086	hsa-miR-513a-5p	PAR-CLIP	23592263
MIRT456091	hsa-miR-6758-5p	PAR-CLIP	23592263
MIRT456092	hsa-miR-6856-5p	PAR-CLIP	23592263
MIRT456090	hsa-miR-6873-5p	PAR-CLIP	23592263
MIRT456089	hsa-miR-3927-3p	PAR-CLIP	23592263
MIRT456088	hsa-miR-6831-5p	PAR-CLIP	23592263
MIRT456087	hsa-miR-4451	PAR-CLIP	23592263
MIRT456086	hsa-miR-513a-5p	PAR-CLIP	23592263
MIRT1126978	hsa-miR-30a	CLIP-seq
MIRT1126979	hsa-miR-30b	CLIP-seq
MIRT1126980	hsa-miR-30c	CLIP-seq
MIRT1126981	hsa-miR-30d	CLIP-seq
MIRT1126982	hsa-miR-30e	CLIP-seq
MIRT1126983	hsa-miR-3927	CLIP-seq
MIRT1126984	hsa-miR-494	CLIP-seq
MIRT1126985	hsa-miR-618	CLIP-seq
MIRT2035957	hsa-miR-21	CLIP-seq
MIRT2035958	hsa-miR-3157-5p	CLIP-seq
MIRT2035959	hsa-miR-34c-3p	CLIP-seq
MIRT2035960	hsa-miR-4691-3p	CLIP-seq
MIRT2035961	hsa-miR-4804-3p	CLIP-seq
MIRT2035962	hsa-miR-590-5p	CLIP-seq
MIRT2035963	hsa-miR-624	CLIP-seq
MIRT1126983	hsa-miR-3927	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005794	Component	Golgi apparatus	IDA
GO:0005813	Component	Centrosome	IDA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IEA
GO:0007283	Process	Spermatogenesis	IEA
GO:0008584	Process	Male gonad development	IEA
GO:0008584	Process	Male gonad development	IEP	17848411
GO:0016604	Component	Nuclear body	IBA
GO:0016604	Component	Nuclear body	IDA
GO:0048515	Process	Spermatid differentiation	IEA

Other IDs

• MIM: 300120
• HGNC: 2568
• e!Ensembl: ENSG00000013619

Protein

• UniProt ID: Q13495
• Protein name: Mastermind-like domain-containing protein 1 (F18) (Protein CG1)
• Protein function: Transactivates the HES3 promoter independently of NOTCH proteins. HES3 is a non-canonical NOTCH target gene which lacks binding sites for RBPJ.
• Tissue specificity: TISSUE SPECIFICITY: Expressed in fetal brain, fetal ovary and fetal testis. Expressed in adult brain, ovary, skin, testis, uterus. Highly expressed in skeletal muscle. {ECO:0000269|PubMed:18162467}.
• Sequence:

  MDDWKSRLVIKSMLPHFAMVGNRQEPRKLQESGKKPSWMEEEDLSFLYKSSPGRKHQGTV
  KRRQEEDHFQFPDMADGGYPNKIKRPCLEDVTLAMGPGAHPSTACAELQVPPLTINPSPA
  AMGVAGQSLLLENNPMNGNIMGSPFVVPQTTEVGLKGPTVPYYEKINSVPAVDQELQELL
  EELTKIQDPSPNELDLEKILGTKPEEPLVLDHPQATLSTTPKPSVQMSHLESLASSKEFA
  SSCSQVTGMSLQIPSSSTGISYSIPSTSKQIVSPSSSMAQSKSQVQAMLPVALPPLPVPQ
  WHHAHQLKALAASKQGSATKQQGPTPSWSGLPPPGLSPPYRPVPSPHPPPLPLPPPPPPF
  SPQSLMVSCMSSNTLSGSTLRGSPNALLSSMTSSSNAALGPAMPYAPEKLPSPALTQQPQ
  FGPQSSILANLMSSTIKTPQGHLMSALPASNPGPSPPYRPEKLSSPGLPQQSFTPQCSLI
  RSLTPTSNLLSQQQQQQQQQQQANVIFKPISSNSSKTLSMIMQQGMASSSPGATEPFTFG
  NTKPLSHFVSEPGPQKMPSMPTTSRQPSLLHYLQQPTPTQASSATASSTATATLQLQQQQ
  QQQQQQPDHSSFLLQQMMQQPQRFQRSVASDSMPALPRQGCCHLFAWTSAASSVKPQHQH
  GNSFTSRQDPQPGDVSPSNITHVDKACKLGEARHPQVSLGRQPPSCQALGSESFLPGSSF
  AHELARVTSSYSTSEAAPWGSWDPKAWRQVPAPLLPSCDATARGTEIRSYGNDP

• Sequence length: 774

Pathways

Reactome:

Pre-NOTCH Transcription and Translation
NOTCH1 Intracellular Domain Regulates Transcription
NOTCH2 intracellular domain regulates transcription
Constitutive Signaling by NOTCH1 PEST Domain Mutants
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
Notch-HLH transcription pathway
RUNX3 regulates NOTCH signaling
NOTCH3 Intracellular Domain Regulates Transcription
NOTCH4 Intracellular Domain Regulates Transcription

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
46,XY ovotesticular disorder of sex development	Pathogenic	rs121909495	RCV002254263	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hypospadias 2, X-linked	Pathogenic	rs121909493, rs121909494, rs121909495, rs1135402752	RCV000012377 RCV000012378 RCV000012379 RCV000496996	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Colon adenocarcinoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Disorder of sexual differentiation	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPOSPADIAS	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAMLD1-related disorder	Benign; Conflicting classifications of pathogenicity; Uncertain significance; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Prostate cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
X-LINKED MYOTUBULAR MYOPATHY-ABNORMAL GENITALIA SYNDROME	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
46, XY Disorders of Sex Development	46, XY disorder of sex development	BEFREE	22479329, 23044878, 26580071, 27383042, 27490115		★☆☆☆☆ Found in Text Mining only
Blind vagina	Blind vagina	HPO_DG			★☆☆☆☆ Found in Text Mining only
Byzanthine arch palate	High palate	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebrovascular accident	Stroke	BEFREE	17980240		★☆☆☆☆ Found in Text Mining only
Chronic kidney disease stage 5	Kidney Disease	BEFREE	30367317		★☆☆☆☆ Found in Text Mining only
Contiguous gene syndrome	Contiguous gene syndrome	BEFREE	10449925		★☆☆☆☆ Found in Text Mining only
Cryptorchidism	Cryptorchidism	Pubtator	27383042	Associate	★☆☆☆☆ Found in Text Mining only
Cryptorchidism	Cryptorchidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
DEAFNESS, AUTOSOMAL DOMINANT 5 (disorder)	Deafness	BEFREE	9450185		★☆☆☆☆ Found in Text Mining only
Diabetes	Diabetes	BEFREE	17980240		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	BEFREE	17980240		★☆☆☆☆ Found in Text Mining only
Disorder of Sex Development 46 XY	46, xy disorder of sex development	Pubtator	22479329, 27383042, 27490115, 33424767	Associate	★☆☆☆☆ Found in Text Mining only
Disorders of Sex Development	Disorders of sex development	Pubtator	22479329, 33424767	Associate	★☆☆☆☆ Found in Text Mining only
Ependymoma	Ependymoma	BEFREE	29354850, 30246434, 31477715		★☆☆☆☆ Found in Text Mining only
Gonadal Dysgenesis	Gonadal Dysgenesis	BEFREE	25660412		★☆☆☆☆ Found in Text Mining only
Granulomatosis with polyangiitis	Granulomatosis With Polyangiitis	BEFREE	30911995		★☆☆☆☆ Found in Text Mining only
Hypogonadism	Hypogonadism	Pubtator	27383042, 35837313	Associate	★☆☆☆☆ Found in Text Mining only
Hypospadias	Hypospadias	BEFREE	17086185, 18162467, 18635673, 18987498, 19339788, 19995686, 20347055, 22030455, 23044878, 25833151, 26815876, 28199199, 29723568		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypospadias	Hypospadias	LHGDN	17086185		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypospadias	Hypospadias	CTD_human_DG	21559465		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypospadias	Hypospadias	Pubtator	22479329, 27383042, 28199199, 35837313	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypospadias 2, X-Linked	Hypospadias, X-Linked	GENOMICS_ENGLAND_DG	17086185, 25660412		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hypospadias 2, X-Linked	Hypospadias, X-Linked	CTD_human_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hypospadias 2, X-Linked	Hypospadias, X-Linked	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hypospadias, balanic	Hypospadias	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypospadias, penoscrotal	Hypospadias	BEFREE	18635673		★☆☆☆☆ Found in Text Mining only
Hypospadias, penoscrotal	Hypospadias	HPO_DG			★☆☆☆☆ Found in Text Mining only
Kidney Failure, Chronic	Kidney Failure	BEFREE	30367317		★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Myeloid leukemia	Pubtator	23147993	Associate	★☆☆☆☆ Found in Text Mining only
Micropenis	Micropenis	BEFREE	18635673		★☆☆☆☆ Found in Text Mining only
Myotubular Myopathy with Abnormal Genital Development	Myotubular Myopathy With Abnormal Genital Development	ORPHANET_DG	26580071, 9169146		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	30911995, 31477715		★☆☆☆☆ Found in Text Mining only
Penile hypospadias	Penile Hypospadias	BEFREE	17086185, 18162467, 18635673, 18987498, 19339788, 19995686, 20347055, 22030455, 22479329, 23044878, 25833151, 26815876, 28199199, 29723568		★☆☆☆☆ Found in Text Mining only
Penile hypospadias	Penile Hypospadias	HPO_DG			★☆☆☆☆ Found in Text Mining only
Penis agenesis	Penis Agenesis	BEFREE	18635673		★☆☆☆☆ Found in Text Mining only
Penis agenesis	Penis Agenesis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Peroxisome biogenesis disorders	Zellweger Syndrome	BEFREE	11330042		★☆☆☆☆ Found in Text Mining only
Pituitary Adenoma	Pituitary adenoma	BEFREE	30911995		★☆☆☆☆ Found in Text Mining only
Polycystic Ovary Syndrome	Polycystic ovary syndrome	Pubtator	37261354	Associate	★☆☆☆☆ Found in Text Mining only
Primary hypogonadism	Hypogonadism	BEFREE	28629181		★☆☆☆☆ Found in Text Mining only
Reifenstein Syndrome	Reifenstein Syndrome	BEFREE	21788424		★☆☆☆☆ Found in Text Mining only
Sex Differentiation Disorders	Sex Differentiation Disorders	BEFREE	23044878, 25833151, 30550360, 31055572		★☆☆☆☆ Found in Text Mining only
Supratentorial Neoplasms	Supratentorial Neoplasm	BEFREE	30246434		★☆☆☆☆ Found in Text Mining only
Swyer Syndrome	Swyer Syndrome	BEFREE	25660412		★☆☆☆☆ Found in Text Mining only
Testicular Neoplasms	Testicular neoplasm	Pubtator	27383042	Associate	★☆☆☆☆ Found in Text Mining only
Turner Syndrome	Turner Syndrome	BEFREE	25660412		★☆☆☆☆ Found in Text Mining only
X-linked centronuclear myopathy	Centronuclear Myopathy, X-Linked	BEFREE	9169146		★☆☆☆☆ Found in Text Mining only
X-linked myotubular myopathy-abnormal genitalia syndrome	Myotubular Myopathy With Abnormal Genital Development	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations