GeneBe

MAMLD1

protein-coding

mastermind like domain containing 1

Gene 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. [provided by RefSeq, Apr 2010]

Previous symbols:
  • CXorf6

MANE transcript

NM_005491.5

Inheritance

XL

ClinVar variants

P:10U:192B:57

Top phenotype

Hypospadias 2, X-linked

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chrX:150,361,422-150,514,178

External References & Databases

Ensembl (ENSG00000013619)NCBI Gene (10046)OMIM (300120)HGNC:2568GenCCUniProt (Q13495)AlphaFoldClinVar (MAMLD1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~152.8 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hypospadias 2, X-linkedSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010423

Submitter: G2P

hypospadias 2, X-linkedSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010423

Submitter: PanelApp Australia

hypospadias 2, X-linkedSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010423

Submitter: Ambry Genetics

hypospadias 2, X-linkedSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010423

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Hypospadias 2, X-linkedXL

Manifestation: Genitourinary

Intervention: General

Rationale: 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

Refs: 17086185Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MAMLD1 variants in ClinVar

7 Conditions Cataloged
not providedTotal: 79
Inborn genetic diseasesTotal: 75
MAMLD1-related disorderTotal: 18
not specifiedTotal: 18
Hypospadias 2, X-linkedTotal: 13
Disorder of sexual differentiationTotal: 1
46,XY ovotesticular disorder of sex developmentTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005491.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
25
clinvar
21
clinvar
11
clinvar
 57
missense
144
clinvar
17
clinvar
8
clinvar
 169
nonsense
5
clinvar
2
clinvar
9
clinvar
 16
start loss
0
frameshift
2
clinvar
1
clinvar
2
clinvar
 5
splice donor/acceptor (+/-2bp)
12
clinvar
 12
Total731923819259

Highest pathogenic variant AF is 0.0000027346737

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 32 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_005491.5RefSeqNP_005482.26MANE Select
ENST00000370401.7EnsemblENSP00000359428.26MANE Select
NM_001177465.3RefSeqNP_001170936.14Standard
NM_001177466.3RefSeqNP_001170937.15Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Disease
  • RUNX3 regulates NOTCH signaling
  • Signal Transduction
  • Gene expression (Transcription)
  • Transcriptional regulation by RUNX3

Biological Process

  • male gonad development

Molecular Function

  • molecular_function

Cellular Component

  • cellular_component
  • nucleoplasm
  • Golgi apparatus
  • centrosome
  • nuclear body

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000432680
Coding exons
4
Length
152760
Individuals with no LoFs
124588
Homozygous LoFs
1
Heterozygous LoFs
0
Defined
124589
p
0.00000401
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.5993303620.9110.00002756497
Missense (PolyPhen)94109.080.861752075
Synonymous-0.8961651511.090.00001272108
Loss of Function3.39420.60.1940.00000155318

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000120.0000089rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec
0.145

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.0709

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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