GDAP2

Summary

GDAP2 (ganglioside induced differentiation associated protein 2, HGNC:18010) is a protein-coding gene on chromosome 1p12, encoding Ganglioside-induced differentiation-associated protein 2 (Q9NXN4).

Predicted to act upstream of or within response to retinoic acid. Located in lysosomal membrane. Implicated in autosomal recessive spinocerebellar ataxia 27.

Source: NCBI Gene 54834 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spinocerebellar ataxia, autosomal recessive 27 (Strong, ClinGen)
• GWAS associations: 4
• Clinical variants (ClinVar): 96 total — 4 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 25
• MANE Select transcript: NM_017686

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18010
Approved symbol	GDAP2
Name	ganglioside induced differentiation associated protein 2
Location	1p12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20142, dJ776P7.1, MACROD3
Ensembl gene	ENSG00000196505
Ensembl biotype	protein_coding
OMIM	618128
Entrez	54834

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000369442, ENST00000369443, ENST00000464026, ENST00000491626, ENST00000493555, ENST00000494224, ENST00000880443, ENST00000880444, ENST00000880445, ENST00000880446

RefSeq mRNA: 2 — MANE Select: NM_017686 NM_001135589, NM_017686

CCDS: CCDS44201, CCDS897

Canonical transcript exons

ENST00000369443 — 14 exons

Exon	Start	End
ENSE00001369845	117929448	117929621
ENSE00001430686	117863485	117870616
ENSE00003463141	117918597	117918736
ENSE00003465134	117911994	117912082
ENSE00003468964	117887698	117887774
ENSE00003476880	117878009	117878152
ENSE00003497530	117886577	117886653
ENSE00003506438	117881823	117881877
ENSE00003544990	117912530	117912683
ENSE00003572020	117896833	117896989
ENSE00003574298	117883488	117883627
ENSE00003638031	117906506	117906582
ENSE00003668510	117899057	117899216
ENSE00003687346	117920182	117920424

Expression profiles

Bgee: expression breadth ubiquitous, 231 present calls, max score 94.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.7054 / max 164.3166, expressed in 1809 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14037	15.0672	1804
14036	4.4845	1623
14034	0.1537	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
caput epididymis	UBERON:0004358	94.41	gold quality
corpus epididymis	UBERON:0004359	93.90	gold quality
cauda epididymis	UBERON:0004360	93.24	gold quality
adrenal tissue	UBERON:0018303	87.57	gold quality
calcaneal tendon	UBERON:0003701	86.89	gold quality
monocyte	CL:0000576	85.86	gold quality
mononuclear cell	CL:0000842	85.53	gold quality
leukocyte	CL:0000738	85.45	gold quality
colonic epithelium	UBERON:0000397	84.43	gold quality
superior surface of tongue	UBERON:0007371	84.26	gold quality
corpus callosum	UBERON:0002336	84.13	gold quality
ganglionic eminence	UBERON:0004023	84.04	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.67	gold quality
islet of Langerhans	UBERON:0000006	83.38	gold quality
bone marrow	UBERON:0002371	83.26	gold quality
ventricular zone	UBERON:0003053	82.99	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.31	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	81.61	gold quality
jejunal mucosa	UBERON:0000399	81.18	gold quality
cortical plate	UBERON:0005343	81.04	gold quality
oral cavity	UBERON:0000167	80.94	gold quality
trabecular bone tissue	UBERON:0002483	80.72	gold quality
rectum	UBERON:0001052	80.59	gold quality
pharyngeal mucosa	UBERON:0000355	80.05	gold quality
sural nerve	UBERON:0015488	80.00	gold quality
stromal cell of endometrium	CL:0002255	79.81	gold quality
mucosa of transverse colon	UBERON:0004991	79.53	gold quality
tongue	UBERON:0001723	79.41	silver quality
body of tongue	UBERON:0011876	79.33	silver quality
biceps brachii	UBERON:0001507	78.81	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-2983	no	2.59
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

240 targeting GDAP2, 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-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7A-5P	99.98	72.29	1790

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	gdap2	ENSDARG00000021569
mus_musculus	Gdap2	ENSMUSG00000027865
rattus_norvegicus	Gdap2	ENSRNOG00000019754
drosophila_melanogaster	Gdap2	FBGN0042135

Paralogs (2): MACROD1 (ENSG00000133315), MACROD2 (ENSG00000172264)

Protein

Protein identifiers

Ganglioside-induced differentiation-associated protein 2 — Q9NXN4 (reviewed: Q9NXN4)

All UniProt accessions (1): Q9NXN4

UniProt curated annotations — full annotation on UniProt →

Disease relevance. Spinocerebellar ataxia, autosomal recessive, 27 (SCAR27) [MIM:618369] A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR27 is a progressive disease characterized by gait difficulties, eye movement abnormalities, dysarthria, and difficulty writing. Some patients may lose independent ambulation. Additional features include spasticity of the lower limbs and cognitive impairment. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the GDAP2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NXN4-1	1	yes
Q9NXN4-2	2

RefSeq proteins (2): NP_001129061, NP_060156* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001251	CRAL-TRIO_dom	Domain
IPR002589	Macro_dom	Domain
IPR035793	Macro_GDAP2	Domain
IPR036865	CRAL-TRIO_dom_sf	Homologous_superfamily
IPR043472	Macro_dom-like	Homologous_superfamily

Pfam: PF01661, PF13716

UniProt features (31 total): helix 11, strand 7, sequence variant 5, domain 2, chain 1, turn 1, region of interest 1, compositionally biased region 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4UML	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NXN4-F1	82.42	0.51

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 280

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 209 (showing top): GOCC_VACUOLAR_MEMBRANE, GTGCCTT_MIR506, CADWELL_ATG16L1_TARGETS_DN, TCCCCAC_MIR491, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_RESPONSE_TO_LIPID, GUO_HEX_TARGETS_DN, TCCAGAG_MIR518C, chr1p12, GOBP_RESPONSE_TO_RETINOIC_ACID, TGCCTTA_MIR124A, FEVR_CTNNB1_TARGETS_UP, GSE5503_PLN_DC_VS_SPLEEN_DC_ACTIVATED_ALLOGENIC_TCELL_DN, ELF2_TARGET_GENES, HDAC4_TARGET_GENES

GO Biological Process (1): response to retinoic acid (GO:0032526)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): lysosomal membrane (GO:0005765)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to lipid	1
response to oxygen-containing compound	1
binding	1
lysosome	1
lytic vacuole membrane	1

Protein interactions and networks

STRING

432 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GDAP2	WDR3	Q9UNX4	616
GDAP2	OARD1	Q9Y530	597
GDAP2	MACROH2A2	Q9P0M6	594
GDAP2	PARP15	Q460N3	584
GDAP2	PARG	Q86W56	566
GDAP2	ADPRS	Q9NX46	500
GDAP2	PARP9	Q8IXQ6	488
GDAP2	CHD1L	Q86WJ1	480
GDAP2	SPAG17	Q6Q759	463
GDAP2	IGSF3	O75054	461
GDAP2	PTGFRN	Q9P2B2	441
GDAP2	TSHZ3	Q63HK5	432
GDAP2	TBX15	Q96SF7	427
GDAP2	HMGCS2	P54868	388
GDAP2	CD58	P19256	375

IntAct

28 interactions, top by confidence:

A	B	Type	Score
VPS29	VPS26C	psi-mi:“MI:0914”(association)	0.760
CEP76	GDAP2	psi-mi:“MI:0915”(physical association)	0.560
GDAP2	CEP76	psi-mi:“MI:0915”(physical association)	0.560
CBY1	CFAP410	psi-mi:“MI:0914”(association)	0.510
GDAP2		psi-mi:“MI:0915”(physical association)	0.490
GDAP2	CFTR	psi-mi:“MI:0915”(physical association)	0.370
VPS35	ILVBL	psi-mi:“MI:0914”(association)	0.350
AHSA1	TOMM40	psi-mi:“MI:0914”(association)	0.350
RAB7A	SCAMP3	psi-mi:“MI:0914”(association)	0.350
VPS35	KIF2A	psi-mi:“MI:0914”(association)	0.350
VPS35	DDX3Y	psi-mi:“MI:0914”(association)	0.350
POLE3	ERI3	psi-mi:“MI:0914”(association)	0.350
ZBED1	SPAG9	psi-mi:“MI:0914”(association)	0.350
REP15	MCM3AP	psi-mi:“MI:0914”(association)	0.350
FBXW11	HNRNPDL	psi-mi:“MI:0914”(association)	0.350
MFSD14A	FAM171A2	psi-mi:“MI:0914”(association)	0.350
CEBPA	HAX1	psi-mi:“MI:0914”(association)	0.350
ERBB2	AP3B1	psi-mi:“MI:0914”(association)	0.350
ATF3	C11orf98	psi-mi:“MI:0914”(association)	0.350
CASP3	C11orf98	psi-mi:“MI:0914”(association)	0.350
CTNNA1	EFCAB5	psi-mi:“MI:0914”(association)	0.350
FOS	MYO1G	psi-mi:“MI:0914”(association)	0.350
GATA2	EFCAB5	psi-mi:“MI:0914”(association)	0.350
GDAP2	BLTP3A	psi-mi:“MI:0915”(physical association)	0.000
GDAP2	CBY1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (27): CEP76 (Two-hybrid), GDAP2 (Affinity Capture-MS), GDAP2 (Affinity Capture-MS), UHRF1BP1 (Affinity Capture-MS), CBY1 (Affinity Capture-MS), GDAP2 (Affinity Capture-RNA), GDAP2 (Affinity Capture-RNA), GDAP2 (Affinity Capture-MS), GDAP2 (Affinity Capture-MS), GDAP2 (Affinity Capture-MS), GDAP2 (Affinity Capture-MS), GDAP2 (Affinity Capture-MS), GDAP2 (Affinity Capture-MS), GDAP2 (Affinity Capture-MS), GDAP2 (Affinity Capture-MS)

ESM2 similar proteins: A0A3L7I2I8, A0FKG7, A2AGL3, A7MB89, B0LPN4, E9Q401, O60733, P30957, P42694, P49754, P97570, P97819, Q15413, Q29RM5, Q2KIX2, Q2T9K6, Q32PW3, Q3SX45, Q4V890, Q59H18, Q5F361, Q5GIG6, Q5KU39, Q5RF15, Q5U2S6, Q5ZKK2, Q66H07, Q66H63, Q6B858, Q6DFV5, Q6NYU2, Q7T3P8, Q7TQP6, Q8C0T1, Q8CEF1, Q8K0L0, Q8K114, Q8TC84, Q91W86, Q92736

Diamond homologs: A0A166ACJ5, A0A559KX76, A1Z1Q3, A4W960, A7MG20, A7T167, A8AI35, B4T2X8, B5F961, B5RBF3, B5XXK9, B7LT90, C9Y0V8, D2TT52, D3RKJ0, D5CE05, E1PL40, E1SDF1, O28751, O59182, P0A8D6, P0A8D7, P0A8D8, P0DC28, P0DC29, P0DN70, P67341, P67342, P67343, P67344, Q0T5Z6, Q292F9, Q2KHU5, Q2KIX2, Q32E73, Q3UYG8, Q44020, Q4J9D2, Q5CZL1, Q5HIW9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	4
Uncertain significance	58
Likely benign	8
Benign	5

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
2060050	NM_017686.4(GDAP2):c.757C>T (p.Arg253Ter)	Pathogenic
624618	NM_017686.4(GDAP2):c.946C>T (p.Gln316Ter)	Pathogenic
624619	NM_017686.4(GDAP2):c.1305dup (p.Ser436fs)	Pathogenic
624620	NM_017686.4(GDAP2):c.1198_1199insG (p.His400fs)	Pathogenic
2050821	NM_017686.4(GDAP2):c.1030+1G>T	Likely pathogenic
2636870	NM_017686.4(GDAP2):c.1048C>T (p.Arg350Ter)	Likely pathogenic
3064725	NM_017686.4(GDAP2):c.1107+1G>T	Likely pathogenic
3338091	NM_017686.4(GDAP2):c.134del (p.Pro45fs)	Likely pathogenic

SpliceAI

2781 predictions. Top by Δscore:

Variant	Effect	Δscore
1:117870497:A:AC	donor_gain	1.0000
1:117878007:AC:A	donor_gain	1.0000
1:117878008:CC:C	donor_gain	1.0000
1:117881884:C:CT	acceptor_gain	1.0000
1:117881885:A:T	acceptor_gain	1.0000
1:117883483:CTA:C	donor_loss	1.0000
1:117883484:TAA:T	donor_loss	1.0000
1:117883486:A:C	donor_gain	1.0000
1:117883486:AC:A	donor_loss	1.0000
1:117883487:C:CT	donor_gain	1.0000
1:117883487:CTTGA:C	donor_gain	1.0000
1:117883625:AGCC:A	acceptor_loss	1.0000
1:117883626:GCC:G	acceptor_loss	1.0000
1:117883627:CCTA:C	acceptor_loss	1.0000
1:117883629:T:A	acceptor_loss	1.0000
1:117884433:A:AC	donor_gain	1.0000
1:117884434:C:CC	donor_gain	1.0000
1:117886571:GCTTA:G	donor_loss	1.0000
1:117886572:CTTA:C	donor_loss	1.0000
1:117886573:TTA:T	donor_loss	1.0000
1:117886574:TA:T	donor_loss	1.0000
1:117886576:CCT:C	donor_loss	1.0000
1:117886650:ACACC:A	acceptor_loss	1.0000
1:117886651:CAC:C	acceptor_gain	1.0000
1:117886652:ACC:A	acceptor_loss	1.0000
1:117886654:C:CG	acceptor_loss	1.0000
1:117886655:T:A	acceptor_loss	1.0000
1:117887770:TATAA:T	acceptor_gain	1.0000
1:117887771:ATAA:A	acceptor_gain	1.0000
1:117887771:ATAAC:A	acceptor_loss	1.0000

AlphaMissense

3240 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:117878028:A:T	V476D	1.000
1:117881845:A:T	V427E	0.999
1:117886635:C:G	R350P	0.999
1:117887752:C:G	A326P	0.999
1:117896925:A:C	F287L	0.999
1:117896925:A:T	F287L	0.999
1:117896927:A:G	F287L	0.999
1:117899089:A:G	I255T	0.999
1:117899116:C:T	G246E	0.999
1:117899117:C:A	G246W	0.999
1:117899117:C:G	G246R	0.999
1:117899117:C:T	G246R	0.999
1:117899189:A:C	Y222D	0.999
1:117906573:C:G	R190T	0.999
1:117912556:G:C	C148W	0.999
1:117912566:A:G	L145P	0.999
1:117912578:G:T	A141D	0.999
1:117912579:C:G	A141P	0.999
1:117912608:G:T	P131H	0.999
1:117912671:C:T	G110D	0.999
1:117918704:G:T	A70D	0.999
1:117878030:A:C	F475L	0.998
1:117878030:A:T	F475L	0.998
1:117878032:A:G	F475L	0.998
1:117878073:A:G	L461P	0.998
1:117883569:A:T	V389E	0.998
1:117883618:A:C	Y373D	0.998
1:117886614:C:T	G357E	0.998
1:117886615:C:G	G357R	0.998
1:117886615:C:T	G357R	0.998

dbSNP variants (sampled 300 via entrez): RS1000108078 (1:117890458 A>G,T), RS1000207536 (1:117923978 T>C), RS1000210114 (1:117915094 T>A,C), RS1000260060 (1:117894833 C>A,G), RS1000262659 (1:117871037 A>C,G), RS1000363828 (1:117927671 C>T), RS1000377183 (1:117921022 C>A,G), RS1000379941 (1:117876925 A>C,G), RS1000389018 (1:117884658 A>G), RS1000411274 (1:117877347 T>C), RS1000423082 (1:117888656 T>C,G), RS1000490583 (1:117916286 T>A), RS1000542383 (1:117916507 A>G), RS1000567675 (1:117872167 G>A), RS1000578563 (1:117865578 C>T)

Disease associations

OMIM: gene MIM:618128 | disease phenotypes: MIM:618369

GenCC curated gene-disease

Disease	Classification	Inheritance
spinocerebellar ataxia, autosomal recessive 27	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
spinocerebellar ataxia, autosomal recessive 27	Strong	AR

Mondo (1): spinocerebellar ataxia, autosomal recessive 27 (MONDO:0032706)

Orphanet (0):

HPO phenotypes

25 total (25 of 25 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000473	Torticollis
HP:0000640	Gaze-evoked nystagmus
HP:0000716	Depression
HP:0000718	Aggressive behavior
HP:0000741	Apathy
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001268	Mental deterioration
HP:0001272	Cerebellar atrophy
HP:0001288	Gait disturbance
HP:0001347	Hyperreflexia
HP:0001348	Brisk reflexes
HP:0002015	Dysphagia
HP:0002066	Gait ataxia
HP:0002120	Cerebral cortical atrophy
HP:0002141	Gait imbalance
HP:0002171	Gliosis
HP:0002359	Frequent falls
HP:0002497	Spastic ataxia
HP:0003677	Slowly progressive
HP:0006895	Lower limb hypertonia
HP:0007338	Hypermetric saccades
HP:0008003	Jerky ocular pursuit movements
HP:0025710	Late young adult onset

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005993_62	Mean corpuscular hemoglobin	1.000000e-23
GCST006011_88	Mean corpuscular volume	2.000000e-21
GCST008839_449	Height	9.000000e-09
GCST009391_966	Metabolite levels	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

30 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	2
Valproic Acid	increases expression, decreases expression, decreases methylation	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
manganese chloride	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	increases methylation, affects cotreatment	1
jinfukang	decreases expression	1
NSC 689534	affects binding, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	increases abundance, increases expression	1
Copper	affects binding, increases expression	1
Doxorubicin	decreases expression	1
Manganese	increases expression	1
Oxygen	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Aflatoxin B1	decreases methylation	1
Lactic Acid	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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