MANF

mesencephalic astrocyte derived neurotrophic factor

Basic information

Region (hg38): 3:51385291-51389397

Previous symbols: [ "ARMET" ]

Links

ENSG00000145050NCBI:7873OMIM:601916HGNC:15461Uniprot:P55145AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Diabetes, deafness, developmental delay, and short stature syndromeARAudiologic/Otolaryngologic; EndocrineEarly recognition and treatment of hearing impairment may improve outcomes, including speech and language development; The condition can involve early-onset diabetes mellitus, and awareness may allow early identification and managementAudiologic/Otolaryngologic; Endocrine; Musculoskeletal; Neurologic26077850; 33500254; 34815294

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MANF 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
clinvar
1
missense
17
clinvar
17
nonsense
0
start loss
0
frameshift
0
inframe indel
0
splice donor/acceptor (+/-2bp)
0
splice region
0
non coding
1
clinvar
1
Total 0 0 17 1 1

Variants in MANF

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

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

Position Type Phenotype Significance ClinVar
3-51385326-GGAGGAGGAT-G MANF-related disorder Likely benign (Sep 26, 2019)3038854
3-51385332-G-GGAT MANF-related disorder Likely benign (Apr 12, 2022)3034168
3-51385346-A-T not specified Uncertain significance (Jun 30, 2022)2299429
3-51385347-G-A not specified Uncertain significance (Jul 06, 2024)3542518
3-51385368-G-A not specified Uncertain significance (Jun 10, 2024)3292878
3-51385380-C-T not specified Uncertain significance (Nov 13, 2024)3542517
3-51385406-AGCCGGGCGCTGCG-A Diabetes, deafness, developmental delay, and short stature syndrome Pathogenic (Dec 06, 2023)2664491
3-51385437-G-T Diabetes, deafness, developmental delay, and short stature syndrome Pathogenic (Dec 06, 2023)2664490
3-51386211-G-T not specified Uncertain significance (Nov 09, 2024)3542520
3-51386246-A-G not specified Uncertain significance (Dec 02, 2021)3122603
3-51386266-C-G not specified Uncertain significance (Jun 05, 2023)2522949
3-51386268-C-T not specified Uncertain significance (Nov 21, 2024)2341384
3-51386281-T-G not specified Uncertain significance (Aug 14, 2024)2283119
3-51386295-T-C not specified Uncertain significance (Sep 29, 2023)3122604
3-51386330-C-T not specified Uncertain significance (Nov 20, 2024)3542521
3-51387727-A-C MANF-related disorder Likely benign (Sep 18, 2019)3041102
3-51387783-A-G not specified Uncertain significance (Aug 21, 2024)3542519
3-51387786-A-G not specified Uncertain significance (Sep 29, 2023)3122605
3-51387812-A-G not specified Uncertain significance (Dec 09, 2023)3122606
3-51387859-G-C not specified Uncertain significance (Mar 28, 2024)3292877
3-51388975-T-C MANF-related disorder Likely benign (Dec 19, 2019)3048261
3-51388980-G-C not specified Uncertain significance (Aug 10, 2021)2242334
3-51388998-G-A not specified Uncertain significance (Jun 06, 2022)2294193
3-51389023-C-T Benign (Apr 07, 2018)733337

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
MANFprotein_codingprotein_codingENST00000528157 44351
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.001390.6791245830131245960.0000522
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.6726683.30.7930.000004371173
Missense in Polyphen2142.8750.48979531
Synonymous0.3512830.50.9190.00000153349
Loss of Function0.71457.040.7103.71e-7107

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00005850.0000585
Ashkenazi Jewish0.000.00
East Asian0.00006450.0000556
Finnish0.0002320.000232
European (Non-Finnish)0.00002850.0000266
Middle Eastern0.00006450.0000556
South Asian0.00006840.0000654
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Selectively promotes the survival of dopaminergic neurons of the ventral mid-brain (PubMed:12794311). Modulates GABAergic transmission to the dopaminergic neurons of the substantia nigra (By similarity). Enhances spontaneous, as well as evoked, GABAergic inhibitory postsynaptic currents in dopaminergic neurons (By similarity). Inhibits cell proliferation and endoplasmic reticulum (ER) stress-induced cell death (PubMed:18561914, PubMed:22637475, PubMed:29497057). Retained in the ER/sarcoplasmic reticulum (SR) through association with the endoplasmic reticulum chaperone protein HSPA5 under normal conditions (PubMed:22637475). Up-regulated and secreted by the ER/SR in response to ER stress and hypoxia (PubMed:22637475). Following secretion by the ER/SR, directly binds to 3-O- sulfogalactosylceramide, a lipid sulfatide in the outer cell membrane of target cells (PubMed:29497057). Sulfatide binding promotes its cellular uptake by endocytosis, and is required for its role in alleviating ER stress and cell toxicity under hypoxic and ER stress conditions (PubMed:29497057). {ECO:0000250|UniProtKB:P0C5H9, ECO:0000269|PubMed:12794311, ECO:0000269|PubMed:18561914, ECO:0000269|PubMed:22637475, ECO:0000269|PubMed:29497057}.;
Pathway
Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Hemostasis (Consensus)

Recessive Scores

pRec
0.135

Intolerance Scores

loftool
0.303
rvis_EVS
-0.01
rvis_percentile_EVS
52.85

Haploinsufficiency Scores

pHI
0.285
hipred
N
hipred_score
0.336
ghis
0.578

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
N
gene_indispensability_score
0.114

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Manf
Phenotype
homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);

Zebrafish Information Network

Gene name
manf
Affected structure
ventral thalamus
Phenotype tag
abnormal
Phenotype quality
has fewer parts of type

Gene ontology

Biological process
platelet degranulation;response to unfolded protein;regulation of signaling receptor activity;neuron projection development;dopaminergic neuron differentiation;regulation of response to endoplasmic reticulum stress
Cellular component
extracellular region;extracellular space;nucleus;endoplasmic reticulum;endoplasmic reticulum lumen;cytosol;sarcoplasmic reticulum lumen
Molecular function
RNA binding;growth factor activity;lipid binding