GDAP1L1

Summary

GDAP1L1 (ganglioside induced differentiation associated protein 1 like 1, HGNC:4213) is a protein-coding gene on chromosome 20q13.12, encoding Ganglioside-induced differentiation-associated protein 1-like 1 (Q96MZ0).

The ganglioside GD3 synthase causes cell differentiation with neurite sprouting when transfected into the mouse neuroblastoma cell line Neuro2a. After differentiation, the expression of several genes is upregulated, including one that encodes a protein termed ganglioside-induced differentiation-associated protein 1 (Gdap1). A similar gene was found in humans, and mutations in the human gene are associated with Charcot-Marie-Tooth type 4A disease. The protein encoded by this gene is similar in sequence to the human GDAP1 protein. Several transcript variants encoding different isoforms, as well as a noncoding transcript variant, have been found for this gene.

Source: NCBI Gene 78997 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 52 total
• MANE Select transcript: NM_024034

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4213
Approved symbol	GDAP1L1
Name	ganglioside induced differentiation associated protein 1 like 1
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000124194
Ensembl biotype	protein_coding
Entrez	78997

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 10 protein_coding

ENST00000342560, ENST00000372952, ENST00000438466, ENST00000445952, ENST00000447658, ENST00000537864, ENST00000612599, ENST00000617075, ENST00000902255, ENST00000936870

RefSeq mRNA: 5 — MANE Select: NM_024034 NM_001256737, NM_001256738, NM_001256739, NM_001256740, NM_024034

CCDS: CCDS13328, CCDS74725, CCDS74726, CCDS74727

Canonical transcript exons

ENST00000342560 — 6 exons

Exon	Start	End
ENSE00000844861	44264445	44264559
ENSE00001383939	44278957	44280947
ENSE00001626561	44257153	44257345
ENSE00001659054	44258434	44258607
ENSE00001941947	44247308	44247514
ENSE00003750999	44263230	44263327

Expression profiles

Bgee: expression breadth ubiquitous, 157 present calls, max score 99.00.

FANTOM5 (CAGE): breadth broad, TPM avg 4.8840 / max 583.6642, expressed in 303 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184708	3.9066	286
184706	0.7857	195
184707	0.1917	86

Top tissues by expression

268 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.00	gold quality
ganglionic eminence	UBERON:0004023	98.39	gold quality
prefrontal cortex	UBERON:0000451	93.33	gold quality
right frontal lobe	UBERON:0002810	93.23	gold quality
anterior cingulate cortex	UBERON:0009835	92.39	gold quality
cingulate cortex	UBERON:0003027	92.32	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.63	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.11	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.01	gold quality
cerebellar hemisphere	UBERON:0002245	90.84	gold quality
cerebellar cortex	UBERON:0002129	90.66	gold quality
neocortex	UBERON:0001950	90.15	gold quality
frontal cortex	UBERON:0001870	89.82	gold quality
cerebellum	UBERON:0002037	88.78	gold quality
amygdala	UBERON:0001876	88.57	gold quality
nucleus accumbens	UBERON:0001882	87.57	gold quality
cerebral cortex	UBERON:0000956	87.53	gold quality
telencephalon	UBERON:0001893	85.70	gold quality
ventricular zone	UBERON:0003053	85.12	gold quality
forebrain	UBERON:0001890	85.05	gold quality
brain	UBERON:0000955	84.78	gold quality
embryo	UBERON:0000922	83.87	gold quality
hypothalamus	UBERON:0001898	83.41	gold quality
caudate nucleus	UBERON:0001873	83.17	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.15	gold quality
primary visual cortex	UBERON:0002436	83.10	gold quality
adenohypophysis	UBERON:0002196	83.02	gold quality
temporal lobe	UBERON:0001871	82.46	gold quality
middle temporal gyrus	UBERON:0002771	81.74	gold quality
putamen	UBERON:0001874	81.71	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	14.01
E-HCAD-5	no	13.53
E-ANND-3	no	2.45

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

70 targeting GDAP1L1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085

Literature-anchored findings (GeneRIF, showing 1)

• Psoriasiform Inflammation Is Associated with Mitochondrial Fission/GDAP1L1 Signaling in Macrophages. (PMID:34638757)

Cross-species orthologs

34 orthologs

Organism	Symbol	Gene ID
danio_rerio	gdap1l1	ENSDARG00000028628
mus_musculus	Gdap1l1	ENSMUSG00000017943
rattus_norvegicus	Gdap1l1	ENSRNOG00000008790
drosophila_melanogaster	GstD1	FBGN0001149
drosophila_melanogaster	GstD2	FBGN0010038
drosophila_melanogaster	GstD3	FBGN0010039
drosophila_melanogaster	GstD4	FBGN0010040
drosophila_melanogaster	GstD5	FBGN0010041
drosophila_melanogaster	GstD6	FBGN0010042
drosophila_melanogaster	GstD7	FBGN0010043
drosophila_melanogaster	GstD8	FBGN0010044
drosophila_melanogaster	GstE12	FBGN0027590
drosophila_melanogaster	Clic	FBGN0030529
drosophila_melanogaster	GstT3	FBGN0031117
drosophila_melanogaster	GstE13	FBGN0033381
drosophila_melanogaster	GstE1	FBGN0034335
drosophila_melanogaster	GstE11	FBGN0034354
drosophila_melanogaster	GstD9	FBGN0038020
drosophila_melanogaster	GstD10	FBGN0042206
drosophila_melanogaster	GstT1	FBGN0050000
drosophila_melanogaster	GstT2	FBGN0050005
drosophila_melanogaster	GstE9	FBGN0063491
drosophila_melanogaster	GstE8	FBGN0063492
drosophila_melanogaster	GstE7	FBGN0063493
drosophila_melanogaster	GstE6	FBGN0063494
drosophila_melanogaster	GstE5	FBGN0063495
drosophila_melanogaster	GstE4	FBGN0063496
drosophila_melanogaster	GstE3	FBGN0063497
drosophila_melanogaster	GstE2	FBGN0063498
drosophila_melanogaster	GstE10	FBGN0063499
caenorhabditis_elegans	exc-4	WBGENE00001365
caenorhabditis_elegans		WBGENE00001371
caenorhabditis_elegans	gst-43	WBGENE00001791
caenorhabditis_elegans		WBGENE00021817

Paralogs (14): GSTO2 (ENSG00000065621), GSTT2 (ENSG00000099984), GSTZ1 (ENSG00000100577), GDAP1 (ENSG00000104381), CLIC5 (ENSG00000112782), GSTT2B (ENSG00000133433), GSTO1 (ENSG00000148834), CLIC2 (ENSG00000155962), CLIC6 (ENSG00000159212), CLIC4 (ENSG00000169504), CLIC3 (ENSG00000169583), CLIC1 (ENSG00000213719), EEF1G (ENSG00000254772), GSTT4 (ENSG00000276950)

Protein

Protein identifiers

Ganglioside-induced differentiation-associated protein 1-like 1 — Q96MZ0 (reviewed: Q96MZ0)

All UniProt accessions (6): A0A087WWT8, Q96MZ0, H0UIB3, H0Y6A7, Q5TE58, Q5TE61

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the GST superfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96MZ0-1	1	yes
Q96MZ0-2	2
Q96MZ0-4	3

RefSeq proteins (5): NP_001243666, NP_001243667, NP_001243668, NP_001243669, NP_076939* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004045	Glutathione_S-Trfase_N	Domain
IPR010987	Glutathione-S-Trfase_C-like	Domain
IPR036249	Thioredoxin-like_sf	Homologous_superfamily
IPR036282	Glutathione-S-Trfase_C_sf	Homologous_superfamily

Pfam: PF13409, PF13410

UniProt features (8 total): splice variant 3, domain 2, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96MZ0-F1	77.88	0.48

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 78 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, GTGCCTT_MIR506, OCT1_03, ACATTCC_MIR1_MIR206, TGACATY_UNKNOWN, CTGYNNCTYTAA_UNKNOWN, MODULE_207, NRSF_01, AACATTC_MIR4093P, MEISSNER_ES_ICP_WITH_H3K4ME3, MEISSNER_BRAIN_ICP_WITH_H3K4ME3, CACTGCC_MIR34A_MIR34C_MIR449, MIKKELSEN_MEF_ICP_WITH_H3K27ME3, AR_Q6, MIKKELSEN_ES_ICP_WITH_H3K4ME3

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (2): mitochondrion (GO:0005739), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1190 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GDAP1L1	FIS1	Q9Y3D6	554
GDAP1L1	MFN2	O95140	531
GDAP1L1	MFF	Q9GZY8	530
GDAP1L1	TMEM47	Q9BQJ4	438
GDAP1L1	CPXM1	Q96SM3	433
GDAP1L1	MIEF2	Q96C03	433
GDAP1L1	DNM1L	O00429	431
GDAP1L1	TMEM176A	Q96HP8	418
GDAP1L1	TMEM176B	Q3YBM2	416
GDAP1L1	TMEM151A	Q8N4L1	413
GDAP1L1	RNMT	O43148	411
GDAP1L1	MIEF1	Q9NQG6	404
GDAP1L1	DHTKD1	Q96HY7	395
GDAP1L1	FZD2	Q14332	379
GDAP1L1	PLTP	P55058	377

IntAct

6 interactions, top by confidence:

A	B	Type	Score
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
VCP	FAM171A2	psi-mi:“MI:0914”(association)	0.350
LCOR	GDAP1L1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (4): GDAP1L1 (Affinity Capture-RNA), GDAP1L1 (Proximity Label-MS), GDAP1L1 (Two-hybrid), GDAP1L1 (Affinity Capture-MS)

ESM2 similar proteins: A2A825, A2VE14, A9CQL8, D3ZVR7, P28801, P47802, Q0VCJ8, Q0VD18, Q0VD27, Q27HK4, Q29RZ1, Q2TBS1, Q3SZB3, Q3U129, Q4R3I0, Q58CY6, Q5H8A4, Q5I0D5, Q5NVN7, Q5R7S9, Q5R8R5, Q5RAJ8, Q5VYX0, Q5ZIL9, Q5ZJB7, Q5ZMH6, Q67FW5, Q6AXQ0, Q6GV29, Q7RTV5, Q86XA0, Q86XW9, Q8BGB7, Q8N8L6, Q8NB37, Q8TBF2, Q91YQ7, Q96G75, Q96MZ0, Q9BU20

Diamond homologs: A6QQZ0, O88741, P04907, P28342, P57108, Q03425, Q8TB36, Q8VE33, Q96MZ0, Q9ZVQ3, Q9ZVQ4, A0A0H3CDY2, A2XMN2, B3FWR8, D2YW48, O04437, O09131, O43123, O43708, O77462, O77473, O80662, O80852, O86043, P0CG29, P12653, P20432, P23202, P25317, P28338, P30104, P30106, P30107, P30108, P30110, P30347, P30568, P30711, P30713, P32110

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

52 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

972 predictions. Top by Δscore:

Variant	Effect	Δscore
20:44247510:AGAAG:A	donor_loss	1.0000
20:44247511:GAAG:G	donor_gain	1.0000
20:44247512:AAGG:A	donor_loss	1.0000
20:44247515:GTAGA:G	donor_loss	1.0000
20:44247516:T:G	donor_loss	1.0000
20:44247553:G:GT	donor_gain	1.0000
20:44257342:GGAG:G	donor_gain	1.0000
20:44257343:GAG:G	donor_gain	1.0000
20:44257343:GAGG:G	donor_gain	1.0000
20:44257346:G:C	donor_loss	1.0000
20:44258608:G:GG	donor_gain	1.0000
20:44263225:CCCA:C	acceptor_loss	1.0000
20:44263226:CCA:C	acceptor_loss	1.0000
20:44263228:A:AG	acceptor_gain	1.0000
20:44263229:G:GA	acceptor_loss	1.0000
20:44263229:G:GG	acceptor_gain	1.0000
20:44263229:GGAC:G	acceptor_gain	1.0000
20:44263324:CATGG:C	donor_loss	1.0000
20:44263325:ATGG:A	donor_loss	1.0000
20:44263326:TGG:T	donor_loss	1.0000
20:44263327:GGT:G	donor_loss	1.0000
20:44263328:G:GA	donor_loss	1.0000
20:44263328:G:GG	donor_gain	1.0000
20:44263329:T:A	donor_loss	1.0000
20:44264440:CCCA:C	acceptor_loss	1.0000
20:44264441:CCA:C	acceptor_loss	1.0000
20:44264442:CA:C	acceptor_loss	1.0000
20:44264443:A:AC	acceptor_loss	1.0000
20:44264443:A:AG	acceptor_gain	1.0000
20:44264443:AG:A	acceptor_gain	1.0000

AlphaMissense

2409 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:44257160:T:C	L63P	1.000
20:44257237:T:C	F89L	1.000
20:44257238:T:C	F89S	1.000
20:44257239:C:A	F89L	1.000
20:44257239:C:G	F89L	1.000
20:44257268:C:A	P99H	1.000
20:44257268:C:G	P99R	1.000
20:44257271:T:A	V100D	1.000
20:44258538:G:C	G160R	1.000
20:44258539:G:A	G160D	1.000
20:44258590:C:A	A177D	1.000
20:44264533:T:C	L245P	1.000
20:44279031:C:A	R279S	1.000
20:44279032:G:C	R279P	1.000
20:44279035:T:C	L280P	1.000
20:44279040:T:C	F282L	1.000
20:44279042:C:A	F282L	1.000
20:44279042:C:G	F282L	1.000
20:44279046:G:A	G284R	1.000
20:44279046:G:C	G284R	1.000
20:44279047:G:A	G284E	1.000
20:44279047:G:T	G284V	1.000
20:44279241:G:C	G349R	1.000
20:44279242:G:A	G349D	1.000
20:44279251:G:A	G352D	1.000
20:44279269:C:A	A358D	1.000
20:44247480:T:C	L49P	0.999
20:44247482:T:G	Y50D	0.999
20:44247488:T:A	W52R	0.999
20:44247488:T:C	W52R	0.999

dbSNP variants (sampled 300 via entrez): RS1000262789 (20:44255982 C>A,T), RS1000368666 (20:44250664 T>C), RS1000390906 (20:44267607 T>A,C), RS1000485882 (20:44268060 C>T), RS1000497856 (20:44257645 G>A,C), RS1000565778 (20:44256491 A>C,G), RS1000575086 (20:44263880 A>C), RS1000594023 (20:44263696 T>C,G), RS1000702782 (20:44262539 G>A), RS1000707484 (20:44252031 G>A), RS1000734264 (20:44257038 C>A,T), RS1000802133 (20:44255511 C>CAGG), RS1000882839 (20:44245329 T>C), RS1000914330 (20:44245908 T>C), RS1000956214 (20:44257904 G>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
sodium arsenite	affects methylation, increases expression	2
entinostat	increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
ethyl-p-hydroxybenzoate	decreases expression	1
terbufos	increases methylation	1
mercuric bromide	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
belinostat	increases expression, affects cotreatment	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Fonofos	increases methylation	1
Estradiol	decreases expression	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Vitamin E	decreases expression	1
Isotretinoin	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.