ADAM29

Summary

ADAM29 (ADAM metallopeptidase domain 29, HGNC:207) is a protein-coding gene on chromosome 4q34.1, encoding Disintegrin and metalloproteinase domain-containing protein 29 (Q9UKF5). May be involved in spermatogenesis and fertilization.

This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. The protein encoded by this gene is highly expressed in testis and may be involved in human spermatogenesis. Alternative splicing results in multiple transcript variants that encode the same protein.

Source: NCBI Gene 11086 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 135 total — 4 pathogenic, 1 likely-pathogenic
• GTEx eGene: eQTL in 5 tissues, sQTL in 1 (q < 0.05)
• Constraint (gnomAD): pLI 0.01 (LoF-tolerant), LOEUF 1.94 (unconstrained)
• MANE Select transcript: NM_014269
• Notable: 135 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:207
Approved symbol	ADAM29
Name	ADAM metallopeptidase domain 29
Location	4q34.1
Locus type	gene with protein product
Status	Approved
Aliases	svph1, CT73
Ensembl gene	ENSG00000168594
Ensembl biotype	protein_coding
OMIM	604778
Entrez	11086

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 4 protein_coding_CDS_not_defined, 1 retained_intron

MANE Select: ENST00000359240

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 3, TSL 3: 1, TSL 4: 5, TSL 5: 2

ENST00000359240, ENST00000404450, ENST00000445694, ENST00000502305, ENST00000502940, ENST00000505141, ENST00000507652, ENST00000507969, ENST00000510280, ENST00000513477, ENST00000514159, ENST00000515538, ENST00000615367, ENST00000618444

RefSeq mRNA: 7 — MANE Select: NM_014269 NM_001130703, NM_001130704, NM_001130705, NM_001278125, NM_001278126, NM_001278127, NM_014269

CCDS: CCDS3823

Canonical transcript exons

ENST00000359240 — 5 exons

Exon	Start	End
ENSE00001402920	174936933	174937013
ENSE00001405560	174930986	174931174
ENSE00001479503	174920687	174920792
ENSE00001559522	174918358	174918471
ENSE00003826702	174975346	174978180

Expression profiles

Bgee: expression breadth broad, 89 present calls, max score 93.88.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0773 / max 65.8584, expressed in 5 samples.

Highest expression (Bgee): sperm, male germ cell, testis, male germ line stem cell (sensu Vertebrata) in testis, endothelial cell.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ADAM29 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 5 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

6 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Tibial	eqtl	6.0e-18	+1.01	4:175403265:G:C
Testis	sqtl	1.1e-08	+0.56	4:175006907:T:C
Artery Aorta	eqtl	1.6e-04	+0.72	4:175403265:G:C
Lung	eqtl	4.4e-04	-0.35	4:175429109:C:T
Brain Nucleus accumbens basal ganglia	eqtl	1.8e-03	+0.37	4:174877813:G:A
Pituitary	eqtl	2.1e-02	+0.38	4:174851815:T:A

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
50688	0.0358	3
50686	0.0101	3
50683	0.0090	3
50689	0.0077	3
50685	0.0076	3
50687	0.0071	3

Top tissues by expression

showing 100 of 246 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	93.88	gold quality
male germ cell	CL:0000015	91.49	gold quality
left testis	UBERON:0004533	90.82	gold quality
right testis	UBERON:0004534	90.20	gold quality
testis	UBERON:0000473	87.99	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.51	gold quality
endothelial cell	CL:0000115	73.89	gold quality
adult organism	UBERON:0007023	71.54	gold quality
buccal mucosa cell	CL:0002336	70.84	silver quality
olfactory bulb	UBERON:0002264	66.36	gold quality
superficial temporal artery	UBERON:0001614	65.58	gold quality
epithelium of nasopharynx	UBERON:0001951	62.85	gold quality
gingival epithelium	UBERON:0001949	62.59	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	62.37	gold quality
cerebellar vermis	UBERON:0004720	62.31	gold quality
diaphragm	UBERON:0001103	61.71	gold quality
parotid gland	UBERON:0001831	60.23	gold quality
lower lobe of lung	UBERON:0008949	59.63	silver quality
gluteal muscle	UBERON:0002000	59.14	gold quality
triceps brachii	UBERON:0001509	59.02	gold quality
vastus lateralis	UBERON:0001379	58.90	gold quality
quadriceps femoris	UBERON:0001377	58.89	gold quality
gingiva	UBERON:0001828	58.88	gold quality
germinal epithelium of ovary	UBERON:0001304	58.85	gold quality
upper leg skin	UBERON:0004262	58.29	silver quality
mucosa of paranasal sinus	UBERON:0005030	58.28	gold quality
islet of Langerhans	UBERON:0000006	58.26	gold quality
amniotic fluid	UBERON:0000173	58.06	gold quality
biceps brachii	UBERON:0001507	58.02	gold quality
secondary oocyte	CL:0000655	57.83	gold quality
cardia of stomach	UBERON:0001162	57.56	gold quality
Brodmann (1909) area 23	UBERON:0013554	56.99	gold quality
middle temporal gyrus	UBERON:0002771	56.88	gold quality
mammalian vulva	UBERON:0000997	56.00	gold quality
nasal cavity epithelium	UBERON:0005384	55.31	gold quality
substantia nigra pars compacta	UBERON:0001965	55.17	silver quality
skin of hip	UBERON:0001554	55.01	gold quality
nipple	UBERON:0002030	54.89	gold quality
heart right ventricle	UBERON:0002080	54.71	gold quality
deltoid	UBERON:0001476	54.52	gold quality
inferior vagus X ganglion	UBERON:0005363	54.44	gold quality
ventral tegmental area	UBERON:0002691	54.41	gold quality
mammary duct	UBERON:0001765	54.23	gold quality
epithelium of mammary gland	UBERON:0003244	54.07	gold quality
thymus	UBERON:0002370	53.82	gold quality
dorsal plus ventral thalamus	UBERON:0001897	53.81	gold quality
trachea	UBERON:0003126	53.73	gold quality
superior surface of tongue	UBERON:0007371	53.73	gold quality
myocardium	UBERON:0002349	53.53	gold quality
pylorus	UBERON:0001166	53.46	gold quality
lateral globus pallidus	UBERON:0002476	53.45	gold quality
subthalamic nucleus	UBERON:0001906	53.30	gold quality
jejunal mucosa	UBERON:0000399	53.26	gold quality
cortical plate	UBERON:0005343	53.17	gold quality
superior vestibular nucleus	UBERON:0007227	52.98	gold quality
synovial joint	UBERON:0002217	52.97	gold quality
renal medulla	UBERON:0000362	52.96	gold quality
lateral nuclear group of thalamus	UBERON:0002736	52.96	gold quality
substantia nigra pars reticulata	UBERON:0001966	52.84	gold quality
trabecular bone tissue	UBERON:0002483	52.80	gold quality
jejunum	UBERON:0002115	52.69	gold quality
trigeminal ganglion	UBERON:0001675	52.60	gold quality
cauda epididymis	UBERON:0004360	52.60	gold quality
urethra	UBERON:0000057	52.47	gold quality
caput epididymis	UBERON:0004358	52.46	gold quality
layer of synovial tissue	UBERON:0007616	52.44	gold quality
medulla oblongata	UBERON:0001896	52.33	gold quality
dorsal root ganglion	UBERON:0000044	52.21	gold quality
pericardium	UBERON:0002407	52.15	gold quality
pigmented layer of retina	UBERON:0001782	51.94	gold quality
penis	UBERON:0000989	51.71	gold quality
skeletal muscle tissue	UBERON:0001134	51.69	gold quality
pons	UBERON:0000988	51.51	gold quality
pancreatic ductal cell	CL:0002079	51.48	silver quality
pharyngeal mucosa	UBERON:0000355	51.10	gold quality
vena cava	UBERON:0004087	51.01	gold quality
right lung	UBERON:0002167	50.99	gold quality
body of tongue	UBERON:0011876	50.86	silver quality
Brodmann (1909) area 46	UBERON:0006483	50.10	gold quality
seminal vesicle	UBERON:0000998	49.97	gold quality
epithelial cell of pancreas	CL:0000083	49.72	gold quality
squamous epithelium	UBERON:0006914	49.71	gold quality
kidney epithelium	UBERON:0004819	49.63	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
occipital lobe	UBERON:0002021	49.06	silver quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
tibial artery	UBERON:0007610	48.78	gold quality
popliteal artery	UBERON:0002250	48.68	gold quality
corpus epididymis	UBERON:0004359	48.62	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
oviduct epithelium	UBERON:0004804	48.48	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.89
E-CURD-53	no	64.94

HPA expression

RNA tissue specificity: Tissue enriched

8 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Testis	tissue	38.4
Postcentral gyrus	tissue	0.3
Endometrium 1	tissue	0.2
Locus coeruleus	tissue	0.2
Lymph node	tissue	0.1
Nucleus accumbens	tissue	0.1
Lung	tissue	0.1
Hippocampus	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 134; highest nTPM — Ventromedial nucleus (1.5), Arcuate nucleus (0.4), Blood vessel (0.3), Corticomedial amygdala (0.3), Inferior temporal gyrus (0.3).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting ADAM29 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 31 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-377-5P	99.70	65.28	712
HSA-MIR-6086	99.70	65.38	699
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-4782-5P	98.35	69.33	1474
HSA-MIR-5706	98.35	69.33	1463
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-204-3P	97.80	66.84	1656
HSA-MIR-1255B-2-3P	97.80	67.04	880
HSA-MIR-4646-5P	97.70	66.84	1692
HSA-MIR-4314	97.50	67.30	1369
HSA-MIR-3192-5P	96.98	65.76	1926
HSA-MIR-514A-5P	96.94	65.49	801
HSA-MIR-597-5P	96.82	67.57	732
HSA-MIR-563	96.26	66.13	450
HSA-MIR-4522	95.76	66.23	742
HSA-MIR-380-5P	95.68	67.32	512

Functional genomics

gnomAD constraint: pLI 0.00811, LOEUF 1.94, missense Z 0.826 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000359240 — one region, missense o/e 0.97.

Literature-anchored findings (GeneRIF, showing 5)

• quantification of LPL and ADAM29 gene expression is a strong prognostic indicator in CLL, providing better prognostic assessment than ZAP-70 in advanced stages of the disease (PMID:15802535)
• Results support the use of LPL and ADAM29 gene expression associated to IGHV mutational status for predicting the clinical outcome of patients treated by oral fludarabine + cyclophosphamide and could be considered for treatment strategies. (PMID:19340428)
• mutated ADAM27 and ADAM7 genes could play a role in melanoma progression. (PMID:21618342)
• PCMC expression of ADAM29, FLRT2, and SLC18A3 could be assessed as part of a routine screen to help identify individuals at risk of severe Obstructive sleep apnea in Asian populations (PMID:24732660)
• Increased transcript expression of ADAM29 was observed in breast cancer tissues compared to normal ones. The expression of ADAM29 and its mutations in different domains significantly influenced proliferation, migration and invasion of breast cancer cells in vitro. (PMID:26977022)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	adam10b	ENSDARG00000015502
danio_rerio	adam10a	ENSDARG00000053468
danio_rerio	adam9b	ENSDARG00000057138
danio_rerio	si:ch1073-396h14.1	ENSDARG00000057590
mus_musculus	Adam29	ENSMUSG00000046258
drosophila_melanogaster	mmd	FBGN0259110
drosophila_melanogaster	kuz	FBGN0259984
caenorhabditis_elegans	sup-17	WBGENE00006324
caenorhabditis_elegans		WBGENE00006804

Paralogs (20): ADAM22 (ENSG00000008277), ADAM28 (ENSG00000042980), ADAM7 (ENSG00000069206), ADAM11 (ENSG00000073670), ADAM2 (ENSG00000104755), ADAM23 (ENSG00000114948), ADAM20 (ENSG00000134007), ADAMDEC1 (ENSG00000134028), ADAM30 (ENSG00000134249), ADAM19 (ENSG00000135074), ADAM10 (ENSG00000137845), ADAM21 (ENSG00000139985), ADAM15 (ENSG00000143537), ADAM12 (ENSG00000148848), ADAM33 (ENSG00000149451), ADAM8 (ENSG00000151651), ADAM17 (ENSG00000151694), ADAM9 (ENSG00000168615), ADAM18 (ENSG00000168619), ADAM32 (ENSG00000197140)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2676326) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 10 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased circulating phosphate level	1
abnormal hepatocyte morphology	1
increased inflammatory response	1
enhanced wound healing	1
increased energy expenditure	1
increased oxygen consumption	1
decreased susceptibility to diet-induced obesity	1
increased carbon dioxide production	1
increased respiratory quotient	1
decreased susceptibility to diet-induced hepatic steatosis	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Rattus norvegicus	Q9Z1K9	98.4%	Diamond
Trichophyton benhamiae CBS 112371	D4B1G0	97.9%	Diamond
Trichophyton verrucosum HKI 0517	D4DCV9	97.9%	Diamond
Bos taurus	Q10741	97.1%	Diamond
Crotalus atrox	A2CJE4	93.8%	Diamond
Macaca fascicularis	Q95194	92.0%	Diamond
Sus scrofa	O77636	90.5%	Diamond
Bothrops jararaca	Q0NZX9	83.7%	Diamond
Xenopus laevis	Q9PSZ3	77.8%	Diamond
Oryctolagus cuniculus	Q28660	64.6%	Diamond
Aspergillus fumigatus Af293	Q4WQ08	57.3%	Diamond
Cavia porcellus	Q60411	56.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
GLRA3	protein-coding	8001

Protein

Protein identifiers

Disintegrin and metalloproteinase domain-containing protein 29 — Q9UKF5 (reviewed: Q9UKF5)

Alternative names: Cancer/testis antigen 73

All UniProt accessions (5): Q9UKF5, A0A140VJD8, D6RBU0, D6RHU0, D6RIU9

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in spermatogenesis and fertilization. Seems to be a non catalytic metalloprotease-like protein.

Subcellular location. Membrane.

Tissue specificity. Expressed specifically in testes.

Disease relevance. Has been found to be frequently mutated in melanoma. ADAM7 mutations may play a role in melanoma progression and metastasis.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UKF5-1	Alpha	yes
Q9UKF5-2	Beta
Q9UKF5-3	Gamma

RefSeq proteins (7): NP_001124175, NP_001124176, NP_001124177, NP_001265054, NP_001265055, NP_001265056, NP_055084* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001590	Peptidase_M12B	Domain
IPR001762	Disintegrin_dom	Domain
IPR002870	Peptidase_M12B_N	Domain
IPR006586	ADAM_Cys-rich	Domain
IPR018358	Disintegrin_CS	Conserved_site
IPR024079	MetalloPept_cat_dom_sf	Homologous_superfamily
IPR034027	Reprolysin_adamalysin	Domain
IPR036436	Disintegrin_dom_sf	Homologous_superfamily

Pfam: PF00200, PF01421, PF01562, PF08516

UniProt features (64 total): sequence variant 17, repeat 9, glycosylation site 9, disulfide bond 7, sequence conflict 6, splice variant 3, domain 3, region of interest 2, compositionally biased region 2, topological domain 2, signal peptide 1, propeptide 1, chain 1, transmembrane region 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UKF5-F1	77.07	0.50

Human Protein Atlas

Protein class: Predicted membrane proteins, Predicted intracellular proteins, Disease related genes

Protein evidence: Evidence at protein level

Functional residue map

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

Disulfide bonds (7)

Type	Positions
Disulfide bond	307–384, 347–369, 349–354, 455–475, 625–636, 630–642, 644–653

Glycosylation sites (9)

Type	Positions
N-linked (glcnac…) asparagine	217, 320, 368, 428, 469, 538, 545, 558, 564

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 51 (showing top): GOMF_METALLOPEPTIDASE_ACTIVITY, XU_GH1_AUTOCRINE_TARGETS_UP, chr4q34, GOCC_CELL_SURFACE, GOBP_MALE_GAMETE_GENERATION, HUTTMANN_B_CLL_POOR_SURVIVAL_DN, GOBP_REPRODUCTIVE_SYSTEM_DEVELOPMENT, GOBP_SEX_DIFFERENTIATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_MALE_SEX_DIFFERENTIATION, GOBP_DEVELOPMENT_OF_PRIMARY_SEXUAL_CHARACTERISTICS, GOCC_SIDE_OF_MEMBRANE, GOBP_PROTEOLYSIS, GOCC_PLASMA_MEMBRANE_REGION, GOMF_PEPTIDASE_ACTIVITY

GO Biological Process (3): proteolysis (GO:0006508), spermatogenesis (GO:0007283), male gonad development (GO:0008584)

GO Molecular Function (3): metalloendopeptidase activity (GO:0004222), metallopeptidase activity (GO:0008237), metal ion binding (GO:0046872)

GO Cellular Component (4): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), sperm head plasma membrane (GO:1990913), membrane (GO:0016020)

GO top-level categories

18 GO namespaces:

Category	Terms
protein metabolic process	1
developmental process involved in reproduction	1
male gamete generation	1
gonad development	1
development of primary male sexual characteristics	1
endopeptidase activity	1
metallopeptidase activity	1
peptidase activity	1
cation binding	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
sperm head	1
sperm plasma membrane	1
plasma membrane region	1
cellular anatomical structure	1

Protein interactions and networks

STRING

showing 16 of 666 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADAM29	FAM135B	Q49AJ0	609
ADAM29	CCDC54	Q8NEL0	483
ADAM29	SEPTIN10	Q9P0V9	372
ADAM29	FAT2	Q9NYQ8	361
ADAM29	ZNF750	Q32MQ0	352
ADAM29	PRSS54	Q6PEW0	332
ADAM29	TEKTIP1	A6NCJ1	323
ADAM29	CIMIP2A	Q6J272	315
ADAM29	MISFA	A0A0U1RRN3	315
ADAM29	CEP44	Q9C0F1	312
ADAM29	XAGE1B	Q9HD64	310
ADAM29	WDR48	Q8TAF3	307
ADAM29	FAT1	Q14517	297
ADAM29	CPXCR1	Q8N123	296
ADAM29	TEX55	Q96M34	295
ADAM29	FLRT2	O43155	295

IntAct

Human interaction partners of ADAM29 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

1 partners by confidence:

Partner	Interaction type	MIscore	Records
PPID	physical association	0.400	1

BioGRID (1 interactions; top human partners by supporting records): PPID (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for ADAM29: 135 ClinVar records (5 pathogenic / likely pathogenic); 9 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	108
Likely benign	20
Benign	0

Top pathogenic / likely-pathogenic (5)

Showing all 5 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
59508	GRCh38/hg38 4q34.1-34.3(chr4:171851295-178772816)x1	Pathogenic	criteria provided, single submitter	1
59512	GRCh38/hg38 4q34.1-35.1(chr4:174080892-183195538)x1	Pathogenic	criteria provided, single submitter	1
635933	Single allele	Pathogenic	criteria provided, single submitter	1
3148912	GRCh37/hg19 4q34.1-34.3(chr4:172781617-182798652)x3	Pathogenic	criteria provided, single submitter	1
2685134	GRCh37/hg19 4q33-35.1(chr4:171476330-184998011)x1	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore ADAM29’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 15 predictions of 608):

Position(s)	Effect	Δscore	Sites
4:174975281	acceptor_gain	0.9800
4:174975344–174975345	acceptor_loss	0.9500	6
4:174918469	donor_gain	0.9400
4:174975339	acceptor_gain	0.9400
4:174975343	acceptor_gain	0.9400
4:174975332	acceptor_loss	0.9100
4:174975282	acceptor_gain	0.8600
4:174934836	donor_gain	0.8500
4:174918479	donor_gain	0.8400
4:174977599	acceptor_gain	0.8400

HPA cancer prognostics

RNA cancer specificity: Not detected

Disease associations

OMIM: gene MIM:604778 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

GWAS associations

9 associations:

Study	Trait	p-value
GCST004988_90	Breast cancer	2e-25
GCST001937_54	Breast cancer	4e-16
GCST003075_118	Cognitive decline rate in late mild cognitive impairment	3e-11
GCST003075_70	Cognitive decline rate in late mild cognitive impairment	6e-11
GCST003075_119	Cognitive decline rate in late mild cognitive impairment	3e-8
GCST003075_12	Cognitive decline rate in late mild cognitive impairment	4e-8
GCST006218_2	Erosive tooth wear (severe vs non-severe)	2e-7
GCST012305_9	Major depressive disorder x sex interaction	4e-6
GCST006226_4	Erosive tooth wear (severe vs none or mild)	5e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0007710	cognitive decline measurement
EFO:0008343	sex interaction measurement

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — M12: Astacin/Adamalysin

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
butyraldehyde	increases expression	1
CGP 52608	affects binding, increases reaction	1
Arsenic Trioxide	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	decreases expression, increases abundance	1
Tetrachlorodibenzodioxin	decreases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 210 trials:

NCT	Phase	Status	Title
NCT04586348	Phase 4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	Phase 4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	Phase 3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	Phase 3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	Phase 3	RECRUITING	Reducing Missed Appointments
NCT07377032	Phase 3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	Phase 2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	Phase 2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	Phase 2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	Phase 1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	Phase 1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	Phase 1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	Phase 2/3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	Phase 2/3	COMPLETED	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	Early Phase 1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	COMPLETED	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice
NCT03381027	Not specified	COMPLETED	BABY SMART (Study of Massage Therapy, Sleep And neurodevelopMenT)
NCT03388294	Not specified	COMPLETED	Evaluation of a Novel Intervention for Infants At Risk for Neurodevelopmental Disorders
NCT03410810	Not specified	UNKNOWN	Childhood Outcomes of Preterm Brain Abnormalities
NCT03492060	Not specified	RECRUITING	Longitudinal Study of Neurogenetic Disorders
NCT03577756	Not specified	COMPLETED	Neurodevelopmental Assessment of Infants With Cystic Fibrosis
NCT03654248	Not specified	COMPLETED	Let’s Get Organized in Adult Psychiatric/habilitation Care
NCT03659279	Not specified	COMPLETED	Let’s Get Organized Feasibility Study
NCT03722615	Not specified	COMPLETED	Epidemiology of Congenital Cytomegalovirus in a High HIV Prevalence Setting, South Africa
NCT03770832	Not specified	ACTIVE_NOT_RECRUITING	Wearable Sensors and Video Recordings to Monitor Motor Development
NCT03830879	Not specified	RECRUITING	Shenzhen Birth Cohort Study
NCT03835689	Not specified	COMPLETED	Strongest FamiliesTM Neurodevelopmental
NCT03882788	Not specified	COMPLETED	The Effect of Anesthesia on Neurodevelopmental Outcome (NDO)
NCT03922087	Not specified	COMPLETED	No-worry Baby Project
NCT03977259	Not specified	ACTIVE_NOT_RECRUITING	Targeting Human Milk Fortification to Improve Preterm Infant Growth and Brain Development
NCT04043572	Not specified	UNKNOWN	The Biomarkers of Neurological Disease in Utero Study
NCT04096430	Not specified	RECRUITING	Evaluation of Effectiveness of Child-oriented Goal-setting in Paediatric Rehabilitation (the ENGAGE Approach)
NCT04108273	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children
NCT04201509	Not specified	COMPLETED	Validity of Neurocognitive Assessment Methods in Childhood ADHD
NCT04233775	Not specified	UNKNOWN	Altered Cerebral Growth and Development in Infants With Congenital Heart Disease
NCT04313283	Not specified	COMPLETED	Translating Peer-to-Peer Support Into a Clinical Setting