MANF
mesencephalic astrocyte derived neurotrophic factor
Basic information
Region (hg38): 3:51385291-51389397
Previous symbols: [ "ARMET" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Diabetes, deafness, developmental delay, and short stature syndrome | AR | Audiologic/Otolaryngologic; Endocrine | Early 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 management | Audiologic/Otolaryngologic; Endocrine; Musculoskeletal; Neurologic | 26077850; 33500254; 34815294 |
ClinVar
This is a list of variants' phenotypes submitted to
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 | |||||
| missense | 17 | 17 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 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) | ||
| 3-51385332-G-GGAT | MANF-related disorder | Likely benign (Apr 12, 2022) | ||
| 3-51385346-A-T | not specified | Uncertain significance (Jun 30, 2022) | ||
| 3-51385347-G-A | not specified | Uncertain significance (Jul 06, 2024) | ||
| 3-51385368-G-A | not specified | Uncertain significance (Jun 10, 2024) | ||
| 3-51385380-C-T | not specified | Uncertain significance (Nov 13, 2024) | ||
| 3-51385406-AGCCGGGCGCTGCG-A | Diabetes, deafness, developmental delay, and short stature syndrome | Pathogenic (Dec 06, 2023) | ||
| 3-51385437-G-T | Diabetes, deafness, developmental delay, and short stature syndrome | Pathogenic (Dec 06, 2023) | ||
| 3-51386211-G-T | not specified | Uncertain significance (Nov 09, 2024) | ||
| 3-51386246-A-G | not specified | Uncertain significance (Dec 02, 2021) | ||
| 3-51386266-C-G | not specified | Uncertain significance (Jun 05, 2023) | ||
| 3-51386268-C-T | not specified | Uncertain significance (Nov 21, 2024) | ||
| 3-51386281-T-G | not specified | Uncertain significance (Aug 14, 2024) | ||
| 3-51386295-T-C | not specified | Uncertain significance (Sep 29, 2023) | ||
| 3-51386330-C-T | not specified | Uncertain significance (Nov 20, 2024) | ||
| 3-51387727-A-C | MANF-related disorder | Likely benign (Sep 18, 2019) | ||
| 3-51387783-A-G | not specified | Uncertain significance (Aug 21, 2024) | ||
| 3-51387786-A-G | not specified | Uncertain significance (Sep 29, 2023) | ||
| 3-51387812-A-G | not specified | Uncertain significance (Dec 09, 2023) | ||
| 3-51387859-G-C | not specified | Uncertain significance (Mar 28, 2024) | ||
| 3-51388975-T-C | MANF-related disorder | Likely benign (Dec 19, 2019) | ||
| 3-51388980-G-C | not specified | Uncertain significance (Aug 10, 2021) | ||
| 3-51388998-G-A | not specified | Uncertain significance (Jun 06, 2022) | ||
| 3-51389023-C-T | Benign (Apr 07, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| MANF | protein_coding | protein_coding | ENST00000528157 | 4 | 4351 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.00139 | 0.679 | 124583 | 0 | 13 | 124596 | 0.0000522 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.672 | 66 | 83.3 | 0.793 | 0.00000437 | 1173 |
| Missense in Polyphen | 21 | 42.875 | 0.48979 | 531 | ||
| Synonymous | 0.351 | 28 | 30.5 | 0.919 | 0.00000153 | 349 |
| Loss of Function | 0.714 | 5 | 7.04 | 0.710 | 3.71e-7 | 107 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000585 | 0.0000585 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000645 | 0.0000556 |
| Finnish | 0.000232 | 0.000232 |
| European (Non-Finnish) | 0.0000285 | 0.0000266 |
| Middle Eastern | 0.0000645 | 0.0000556 |
| South Asian | 0.0000684 | 0.0000654 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- 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
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
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