PEX16

Summary

PEX16 (peroxisomal biogenesis factor 16, HGNC:8857) is a protein-coding gene on chromosome 11p11.2, encoding Peroxisomal membrane protein PEX16 (Q9Y5Y5). Required for peroxisome membrane biogenesis.

The protein encoded by this gene is an integral peroxisomal membrane protein. An inactivating nonsense mutation localized to this gene was observed in a patient with Zellweger syndrome of the complementation group CGD/CG9. Expression of this gene product morphologically and biochemically restores the formation of new peroxisomes, suggesting a role in peroxisome organization and biogenesis. Alternative splicing has been observed for this gene and two variants have been described.

Source: NCBI Gene 9409 — RefSeq curated summary.

At a glance

• Gene–disease (curated): peroxisome biogenesis disorder (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 664 total — 26 pathogenic, 14 likely-pathogenic
• Phenotypes (HPO): 127
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_004813

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8857
Approved symbol	PEX16
Name	peroxisomal biogenesis factor 16
Location	11p11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000121680
Ensembl biotype	protein_coding
OMIM	603360
Entrez	9409

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 9 protein_coding, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000241041, ENST00000378750, ENST00000523721, ENST00000525192, ENST00000525229, ENST00000527371, ENST00000528674, ENST00000529030, ENST00000532554, ENST00000532681, ENST00000533151, ENST00000905948, ENST00000905949, ENST00000938296, ENST00000938297

RefSeq mRNA: 2 — MANE Select: NM_004813 NM_004813, NM_057174

CCDS: CCDS31472, CCDS7917

Canonical transcript exons

ENST00000378750 — 11 exons

Exon	Start	End
ENSE00000824591	45913819	45913938
ENSE00001478608	45909663	45910312
ENSE00002186467	45917700	45917877
ENSE00003500444	45917458	45917493
ENSE00003502038	45915703	45915836
ENSE00003554263	45910898	45910962
ENSE00003589965	45914316	45914468
ENSE00003620215	45916227	45916303
ENSE00003688452	45914604	45914684
ENSE00003689758	45915468	45915568
ENSE00003787572	45914131	45914203

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 94.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.4150 / max 163.6229, expressed in 1817 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
119488	8.0187	1771
119490	6.8974	1771
119494	2.2587	1041
119489	1.8392	1194
119492	1.5133	1049
119493	1.3751	760
119491	0.5126	262

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
prefrontal cortex	UBERON:0000451	94.33	gold quality
granulocyte	CL:0000094	94.20	gold quality
right lobe of liver	UBERON:0001114	94.15	gold quality
adenohypophysis	UBERON:0002196	93.85	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.62	gold quality
body of pancreas	UBERON:0001150	93.35	gold quality
mucosa of transverse colon	UBERON:0004991	93.22	gold quality
endothelial cell	CL:0000115	93.20	gold quality
right frontal lobe	UBERON:0002810	93.04	gold quality
pituitary gland	UBERON:0000007	92.92	gold quality
anterior cingulate cortex	UBERON:0009835	92.72	gold quality
cingulate cortex	UBERON:0003027	92.68	gold quality
body of stomach	UBERON:0001161	92.63	gold quality
mucosa of stomach	UBERON:0001199	92.54	gold quality
ileal mucosa	UBERON:0000331	92.38	gold quality
parotid gland	UBERON:0001831	92.32	gold quality
metanephros cortex	UBERON:0010533	92.24	gold quality
amygdala	UBERON:0001876	92.16	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.07	gold quality
spinal cord	UBERON:0002240	91.94	gold quality
nucleus accumbens	UBERON:0001882	91.87	gold quality
caudate nucleus	UBERON:0001873	91.80	gold quality
putamen	UBERON:0001874	91.70	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.56	gold quality
left adrenal gland cortex	UBERON:0035825	91.40	gold quality
neocortex	UBERON:0001950	91.17	gold quality
frontal cortex	UBERON:0001870	91.16	gold quality
left adrenal gland	UBERON:0001234	91.15	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.10	gold quality
right adrenal gland cortex	UBERON:0035827	91.04	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.65
E-MTAB-6058	no	59.43

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting PEX16, 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-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-5190	99.15	67.76	1234
HSA-MIR-7854-3P	99.08	66.26	1117
HSA-MIR-6878-5P	98.49	67.91	2142
HSA-MIR-4733-3P	98.35	65.20	994
HSA-MIR-6773-3P	98.17	65.51	1213
HSA-MIR-484	98.16	66.92	1074
HSA-MIR-3155A	98.16	66.09	965
HSA-MIR-3155B	98.16	66.09	965
HSA-MIR-134-3P	96.83	66.22	1001

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 7)

• aberrant splicing mutation of the PEX16 gene in patients with Zellweger syndrome (PMID:11890679)
• Pex16p functions in peroxisome membrane assembly, more likely upstream of Pex3p (PMID:12223482)
• PEX16 regulates peroxisome assembly by being cotranslationally inserted into the ER and serving to recruit other peroxisomal membrane proteins to membranes. (PMID:16717127)
• An unusual variant peroxisome biogenesis disorder caused by mutations in the PEX16 gene, with a relatively mild clinical phenotype and an unexpected phenotype in fibroblasts, was identified. (PMID:20647552)
• Data show that knockdown of Sec16B but not Sec16A by RNAi affected the morphology of peroxisomes, inhibited the transport of Pex16 from the ER to peroxisomes, and suppressed expression of Pex3. (PMID:21768384)
• PEX16 mediates the peroxisomal trafficking of two distinct peroxisomal membrane proteins, PEX3 and PMP34, via the endoplasmic reticulum (PMID:25002403)
• Knockdown of PEX16 Induces Autophagic Degradation of Peroxisomes. (PMID:34360754)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pex16	ENSDARG00000058202
mus_musculus	Pex16	ENSMUSG00000027222
rattus_norvegicus	Pex16	ENSRNOG00000006539
drosophila_melanogaster	Pex16	FBGN0037019

Protein

Protein identifiers

Peroxisomal membrane protein PEX16 — Q9Y5Y5 (reviewed: Q9Y5Y5)

Alternative names: Peroxin-16, Peroxisomal biogenesis factor 16

All UniProt accessions (7): E9PLS4, E9PMM3, E9PMS3, E9PP98, E9PQW0, E9PSC6, Q9Y5Y5

UniProt curated annotations — full annotation on UniProt →

Function. Required for peroxisome membrane biogenesis. May play a role in early stages of peroxisome assembly. Can recruit other peroxisomal proteins, such as PEX3 and PMP34, to de novo peroxisomes derived from the endoplasmic reticulum (ER). May function as receptor for PEX3.

Subunit / interactions. Interacts with PEX19.

Subcellular location. Peroxisome membrane.

Disease relevance. Peroxisome biogenesis disorder complementation group 9 (PBD-CG9) [MIM:614876] A peroxisomal disorder arising from a failure of protein import into the peroxisomal membrane or matrix. The peroxisome biogenesis disorders (PBD group) are genetically heterogeneous with at least 14 distinct genetic groups as concluded from complementation studies. Include disorders are: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct from RCDP and constitute a clinical continuum of overlapping phenotypes known as the Zellweger spectrum (PBD-ZSS). The disease is caused by variants affecting the gene represented in this entry. Peroxisome biogenesis disorder 8A (PBD8A) [MIM:614876] A fatal peroxisome biogenesis disorder belonging to the Zellweger disease spectrum and clinically characterized by severe neurologic dysfunction with profound psychomotor retardation, severe hypotonia and neonatal seizures, craniofacial abnormalities, liver dysfunction, and biochemically by the absence of peroxisomes. Additional features include cardiovascular and skeletal defects, renal cysts, ocular abnormalities, and hearing impairment. Most severely affected individuals with the classic form of the disease (classic Zellweger syndrome) die within the first year of life. The disease is caused by variants affecting the gene represented in this entry. Peroxisome biogenesis disorder 8B (PBD8B) [MIM:614877] A relatively mild peroxisome biogenesis disorder. Affected individuals manifest lower limb spasticity and ataxia resulting in wheelchair dependence. Other features include optic atrophy, cataracts, dysarthria, dysphagia, constipation, and a peripheral demyelinating motor and sensory neuropathy. Cognition is relatively preserved. Biochemical abnormalities are mild and include increased very-long-chain fatty acids (VLCFA), increased bile acid intermediates, and increased branched chain fatty acids. Phytanic acid alpha-oxidation, pristanic acid beta-oxidation, and red cell plasmalogen are normal. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the peroxin-16 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y5Y5-1	1	yes
Q9Y5Y5-2	2

RefSeq proteins (2): NP_004804, NP_476515 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013919	Pex16	Family

Pfam: PF08610

UniProt features (21 total): sequence variant 6, region of interest 4, topological domain 3, compositionally biased region 2, sequence conflict 2, transmembrane region 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y5Y5-F1	83.07	0.36

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9603798	Class I peroxisomal membrane protein import

MSigDB gene sets: 383 (showing top): GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_MEMBRANE_BIOGENESIS, ROVERSI_GLIOMA_COPY_NUMBER_UP, GOBP_PROTEIN_TARGETING, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_MEMBRANE_DOCKING, HNF4_DR1_Q3, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, HNF4_01, DOUGLAS_BMI1_TARGETS_DN, GOBP_PEROXISOMAL_TRANSPORT

GO Biological Process (8): protein targeting to peroxisome (GO:0006625), peroxisome organization (GO:0007031), peroxisome membrane biogenesis (GO:0016557), protein import into peroxisome matrix (GO:0016558), protein to membrane docking (GO:0022615), ER-dependent peroxisome organization (GO:0032581), protein import into peroxisome membrane (GO:0045046), ER-dependent peroxisome localization (GO:0106101)

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

GO Cellular Component (6): peroxisome (GO:0005777), peroxisomal membrane (GO:0005778), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Protein localization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
establishment of protein localization to peroxisome	3
protein localization to peroxisome	3
peroxisome organization	2
peroxisomal membrane transport	2
cytoplasm	2
cellular anatomical structure	2
protein targeting	1
organelle organization	1
membrane biogenesis	1
protein transmembrane import into intracellular organelle	1
membrane docking	1
intracellular protein transport	1
protein localization to membrane	1
establishment of protein localization to membrane	1
binding	1
microbody	1
peroxisome	1
microbody membrane	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1

Protein interactions and networks

STRING

1000 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PEX16	PEX19	P40855	987
PEX16	PEX3	P56589	984
PEX16	PEX12	O00623	962
PEX16	PEX10	O60683	962
PEX16	PEX5	P50542	960
PEX16	PEX6	Q13608	959
PEX16	PEX13	Q92968	957
PEX16	PEX7	O00628	955
PEX16	PEX2	P28328	928
PEX16	PEX14	O75381	922
PEX16	PEX26	Q7Z412	918
PEX16	PEX5L	Q8IYB4	900
PEX16	PEX11B	O96011	889
PEX16	ABCD3	P28288	881
PEX16	AGPS	O00116	856

IntAct

144 interactions, top by confidence:

A	B	Type	Score
PEX3	PEX19	psi-mi:“MI:0407”(direct interaction)	0.980
PEX16	PEX19	psi-mi:“MI:0915”(physical association)	0.950
PEX19	PEX16	psi-mi:“MI:2364”(proximity)	0.950
PEX19	PEX16	psi-mi:“MI:0915”(physical association)	0.950
PEX16	PEX19	psi-mi:“MI:2364”(proximity)	0.950
PEX19	PEX16	psi-mi:“MI:0407”(direct interaction)	0.950
PEX16	PEX19	psi-mi:“MI:0407”(direct interaction)	0.950
PEX16	PEX3	psi-mi:“MI:0915”(physical association)	0.750

BioGRID (87): PEX16 (Affinity Capture-MS), PEX19 (Two-hybrid), PEX16 (Affinity Capture-MS), PEX16 (Affinity Capture-MS), PEX16 (Affinity Capture-MS), PEX16 (Affinity Capture-MS), PEX16 (Affinity Capture-MS), PEX16 (Affinity Capture-MS), PEX16 (Affinity Capture-MS), PEX16 (Affinity Capture-MS), PEX16 (Affinity Capture-MS), PEX16 (Affinity Capture-MS), PEX16 (Negative Genetic), PEX16 (FRET), PEX19 (FRET)

ESM2 similar proteins: A0A1D5PJB7, A0A1L8FG46, A0A1L8FM16, A1L134, A4FUD4, B1AUE5, F1MX48, O00623, O60683, O75425, O77759, O88177, O89109, O95870, P0C8N6, P70295, Q0VF94, Q16586, Q17RQ9, Q1JPD2, Q28686, Q49LS1, Q4R8P0, Q5GH56, Q5GH64, Q5GH72, Q5R6S0, Q643R3, Q6MG55, Q86XJ0, Q8BGG6, Q8CB65, Q8HXW8, Q8IUH8, Q8N9W5, Q8VC48, Q924T7, Q95K25, Q96EP0, Q96HA9

Diamond homologs: B0JYZ2, Q2KII7, Q4QRH7, Q550G0, Q6INN0, Q91XC9, Q9Y5Y5, Q8S8S1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 81 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
peroxisome organization	5	56.5×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	26
Likely pathogenic	14
Uncertain significance	213
Likely benign	330
Benign	23

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069798	NM_004813.4(PEX16):c.65_71del (p.Thr22fs)	Pathogenic
1072383	NM_004813.4(PEX16):c.115C>T (p.Arg39Ter)	Pathogenic
1366308	NM_004813.4(PEX16):c.446dup (p.Ala150fs)	Pathogenic
1415802	NM_004813.4(PEX16):c.718C>T (p.Gln240Ter)	Pathogenic
1455420	NM_004813.4(PEX16):c.737G>A (p.Trp246Ter)	Pathogenic
1456790	NM_004813.4(PEX16):c.451C>T (p.Gln151Ter)	Pathogenic
2010587	NM_004813.4(PEX16):c.535C>T (p.Gln179Ter)	Pathogenic
2124910	NM_004813.4(PEX16):c.312G>A (p.Trp104Ter)	Pathogenic
2724609	NM_004813.4(PEX16):c.595C>T (p.Gln199Ter)	Pathogenic
2728726	NM_004813.4(PEX16):c.311G>A (p.Trp104Ter)	Pathogenic
2763578	NM_004813.4(PEX16):c.729G>A (p.Trp243Ter)	Pathogenic
2821361	NM_004813.4(PEX16):c.58del (p.Ala20fs)	Pathogenic
2846416	NM_004813.4(PEX16):c.817G>T (p.Glu273Ter)	Pathogenic
2860761	NM_004813.4(PEX16):c.238C>T (p.Gln80Ter)	Pathogenic
3000652	NM_004813.4(PEX16):c.512C>A (p.Ser171Ter)	Pathogenic
3002716	NM_004813.4(PEX16):c.714G>A (p.Trp238Ter)	Pathogenic
30351	NM_004813.4(PEX16):c.984del (p.Ile330fs)	Pathogenic
30352	NM_004813.4(PEX16):c.992A>G (p.Tyr331Cys)	Pathogenic
30353	NM_004813.4(PEX16):c.952+118_*82del	Pathogenic
3643414	NM_004813.4(PEX16):c.146del (p.Leu49fs)	Pathogenic
4717746	NM_004813.4(PEX16):c.254G>A (p.Trp85Ter)	Pathogenic
4723131	NM_004813.4(PEX16):c.823del (p.Arg275fs)	Pathogenic
4724128	NM_004813.4(PEX16):c.51_52del (p.His18fs)	Pathogenic
4736425	NM_004813.4(PEX16):c.140dup (p.Glu48fs)	Pathogenic
6466	NM_004813.4(PEX16):c.526C>T (p.Arg176Ter)	Pathogenic
6467	NM_004813.4(PEX16):c.952+2T>C	Pathogenic
1067989	NM_004813.4(PEX16):c.887+2T>G	Likely pathogenic
1335949	NM_004813.4(PEX16):c.461-2_461del	Likely pathogenic
1480141	NM_004813.4(PEX16):c.888-2A>C	Likely pathogenic
1510865	NM_004813.4(PEX16):c.694+1G>A	Likely pathogenic

SpliceAI

1480 predictions. Top by Δscore:

Variant	Effect	Δscore
11:45910896:A:AC	donor_gain	1.0000
11:45910897:C:CC	donor_gain	1.0000
11:45910899:TGTG:T	donor_gain	1.0000
11:45913813:GCTTA:G	donor_loss	1.0000
11:45913814:CTTA:C	donor_loss	1.0000
11:45913815:TTA:T	donor_loss	1.0000
11:45913816:TAC:T	donor_loss	1.0000
11:45913817:A:AC	donor_gain	1.0000
11:45913817:A:C	donor_loss	1.0000
11:45913818:C:CT	donor_gain	1.0000
11:45913818:CT:C	donor_gain	1.0000
11:45913818:CTCGG:C	donor_gain	1.0000
11:45913934:TCAGG:T	acceptor_gain	1.0000
11:45913935:CAGG:C	acceptor_gain	1.0000
11:45913935:CAGGC:C	acceptor_gain	1.0000
11:45913936:AGG:A	acceptor_gain	1.0000
11:45913936:AGGC:A	acceptor_loss	1.0000
11:45913937:GG:G	acceptor_gain	1.0000
11:45913938:GCT:G	acceptor_loss	1.0000
11:45913939:C:CA	acceptor_loss	1.0000
11:45913939:C:CC	acceptor_gain	1.0000
11:45913940:T:G	acceptor_loss	1.0000
11:45914393:AGCT:A	donor_gain	1.0000
11:45914394:G:C	donor_gain	1.0000
11:45914464:CGGCG:C	acceptor_gain	1.0000
11:45914592:T:TA	donor_gain	1.0000
11:45914598:ACTTA:A	donor_loss	1.0000
11:45914600:TTACT:T	donor_loss	1.0000
11:45914601:TACTG:T	donor_loss	1.0000
11:45914602:A:AC	donor_gain	1.0000

AlphaMissense

2113 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:45914162:A:G	W246R	0.996
11:45914162:A:T	W246R	0.996
11:45913938:G:C	S256R	0.995
11:45913938:G:T	S256R	0.995
11:45914132:T:G	S256R	0.995
11:45915568:C:A	K120N	0.994
11:45915568:C:G	K120N	0.994
11:45916285:A:G	L56P	0.994
11:45913876:C:G	R277P	0.992
11:45913847:G:T	R287S	0.991
11:45914171:A:G	W243R	0.991
11:45914171:A:T	W243R	0.991
11:45916294:G:T	A53D	0.991
11:45917460:A:G	L49P	0.990
11:45917713:A:C	S33R	0.990
11:45917713:A:T	S33R	0.990
11:45917715:T:G	S33R	0.990
11:45910262:A:G	W335R	0.989
11:45910262:A:T	W335R	0.989
11:45914196:G:C	S234R	0.989
11:45914196:G:T	S234R	0.989
11:45914198:T:G	S234R	0.989
11:45914351:G:T	A220E	0.988
11:45917736:C:T	E26K	0.988
11:45914327:G:T	P228Q	0.986
11:45915805:A:G	L86P	0.986
11:45916269:A:C	N61K	0.986
11:45916269:A:T	N61K	0.986
11:45915557:C:G	R124P	0.985
11:45915773:C:T	E97K	0.985

dbSNP variants (sampled 300 via entrez): RS1000096942 (11:45918537 G>C), RS1000566462 (11:45920406 C>T), RS1001097040 (11:45912075 A>C,T), RS1001184234 (11:45910013 C>A,G,T), RS1001236613 (11:45917451 G>A), RS1001265713 (11:45911715 G>A), RS1001527086 (11:45911881 G>A), RS1001627032 (11:45909319 C>T), RS1002187464 (11:45919202 C>A,G), RS1002440429 (11:45917253 A>C), RS1002472739 (11:45913264 G>A), RS1002805743 (11:45916014 A>G), RS1003196868 (11:45920767 C>G,T), RS1003229850 (11:45920505 C>T), RS1003999809 (11:45910370 CACAT>C,CACATACAT)

Disease associations

OMIM: gene MIM:603360 | disease phenotypes: MIM:214100, MIM:614876, MIM:614877, MIM:251000

GenCC curated gene-disease

Disease	Classification	Inheritance
peroxisome biogenesis disorder 8A (Zellweger)	Definitive	Autosomal recessive
peroxisome biogenesis disorder 8B	Definitive	Autosomal recessive
peroxisome biogenesis disorder	Strong	Autosomal recessive
Zellweger spectrum disorders	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
peroxisome biogenesis disorder	Definitive	AR

Mondo (8): peroxisome biogenesis disorder (MONDO:0019234), peroxisome biogenesis disorder 8A (Zellweger) (MONDO:0013942), peroxisome biogenesis disorder due to PEX16 defect (MONDO:0100269), peroxisome biogenesis disorder 8B (MONDO:0013943), microcephaly (MONDO:0001149), peroxisome biogenesis disorder 1A (Zellweger) (MONDO:0008953), methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency (MONDO:0009612), Zellweger spectrum disorders (MONDO:0019609)

Orphanet (4): Peroxisome biogenesis disorder (Orphanet:79189), Zellweger syndrome (Orphanet:912), Neonatal adrenoleukodystrophy (Orphanet:44), Vitamin B12-unresponsive methylmalonic acidemia (Orphanet:27)

HPO phenotypes

127 total (30 of 127 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000126	Hydronephrosis
HP:0000157	Abnormality of the tongue
HP:0000162	Glossoptosis
HP:0000174	Abnormal palate morphology
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000260	Wide anterior fontanel
HP:0000268	Dolichocephaly
HP:0000271	Abnormality of the face
HP:0000286	Epicanthus
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000377	Abnormal pinna morphology
HP:0000407	Sensorineural hearing impairment
HP:0000431	Wide nasal bridge
HP:0000463	Anteverted nares
HP:0000474	Thickened nuchal skin fold
HP:0000486	Strabismus
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000510	Rod-cone dystrophy
HP:0000518	Cataract

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002115_15	Axial length	2.000000e-06
GCST007825_1	Alzheimer’s disease or fasting glucose levels (pleiotropy)	2.000000e-13
GCST012256_1	SAPHO syndrome	8.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005318	axial length measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D015211	Zellweger Syndrome	C06.552.970; C10.228.140.163.100.968; C12.050.351.968.419.978; C12.200.777.419.978; C12.950.419.978; C16.131.077.970; C16.320.565.189.968; C16.320.565.663.970; C18.452.132.100.968; C18.452.648.189.968; C18.452.648.663.970
C565390	Methylmalonic Aciduria due to Methylmalonyl-CoA Mutase Deficiency (supp.)
C536664	Peroxisome biogenesis disorders (supp.)
C531857	Zellweger leukodystrophy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3774297 (SINGLE PROTEIN)

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
sodium arsenite	increases expression, increases abundance	3
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, increases methylation	1
triphenyl phosphate	affects expression	1
quercitrin	decreases expression	1
monomethylarsonous acid	increases expression	1
abrine	increases expression	1
bisphenol S	decreases methylation	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Arsenic	increases abundance, increases expression	1
Dietary Carbohydrates	decreases expression	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1
Valproic Acid	increases methylation	1
Vitamin E	decreases expression	1
Isotretinoin	decreases expression	1
Antirheumatic Agents	decreases expression	1
Acrylamide	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3778972	Binding	Antagonist activity at CRTH2 receptor (unknown origin) expressed in CHOK1 cells assessed as dissociation half life measured up to 25 hrs by GTPgammaS assay	Structure-activity relationships (SAR) and structure-kinetic relationships (SKR) of sulphone-based CRTh2 antagonists. — Eur J Med Chem

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 finite cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C7Y6	HAP1 PEX16 (-) 1	Cancer cell line	Male
CVCL_C7Y7	HAP1 PEX16 (-) 2	Cancer cell line	Male
CVCL_N050	GM06231	Finite cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00007020	PHASE3	COMPLETED	Compassionate Treatment of Patients With Inborn Errors of Bile Acid Metabolism With Cholic Acid
NCT01838941	PHASE3	COMPLETED	Betaine and Peroxisome Biogenesis Disorders
NCT02171104	PHASE2	ACTIVE_NOT_RECRUITING	MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
NCT03856866	PHASE2	COMPLETED	Hydroxychloroquine Administration for Reduction of Pexophagy
NCT00004442	Not specified	TERMINATED	Study of Bile Acids in Patients With Peroxisomal Disorders
NCT02699190	Not specified	COMPLETED	LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies
NCT03047369	Not specified	RECRUITING	The Myelin Disorders Biorepository Project
NCT01668186	Not specified	RECRUITING	Longitudinal Natural History Study of Patients With Peroxisome Biogenesis Disorders (PBD)
NCT03440905	Not specified	COMPLETED	Proxy-Reported Symptoms and Quality of Life Survey in Zellweger Spectrum Disorders
NCT06190626	Not specified	RECRUITING	Longitudinal Prospective Natural History Study of Retinopathy in Zellweger Spectrum Disorder
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT00001639	Not specified	COMPLETED	Evaluation of Patients With Unresolved Chromosome Abnormalities
NCT01151462	Not specified	WITHDRAWN	Postnatal HCMV Infection in Very Preterm Infants. Implications, Morbidity, Growth and Neurodevelopmental Outcomes.
NCT01565005	Not specified	COMPLETED	Microcephaly Genetic Deficiency in Neural Progenitors
NCT02510170	Not specified	COMPLETED	Fetal and Maternal Head Circumference During Pregnancy in Israeli Population
NCT02741882	Not specified	COMPLETED	Zika and Microcephaly: Case-control Study
NCT02943304	Not specified	COMPLETED	Neurodevelopment Outcome of Newborns Exposed to Zika Virus (ZIKV) in Utero
NCT03255369	Not specified	UNKNOWN	Vertical Exposure to Zika Virus and Its Consequences for Child Neurodevelopment (ZIKVIRUSIFF)
NCT03325946	Not specified	RECRUITING	The FBRI VTC Neuromotor Research Clinic
NCT03330600	Not specified	COMPLETED	Efficacy of Aquatic Physiotherapy in Children With Microcephaly by Zika Virus Congenital Syndrome
NCT03548779	Not specified	COMPLETED	North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT03651687	Not specified	COMPLETED	Guangzhou Surveillance and Clinical Study in Microcephaly (GSCSM)
NCT03922594	Not specified	TERMINATED	Surveillance of Zika-related Microcephaly in Sub-Saharan Africa and Asia
NCT04816175	Not specified	COMPLETED	Intensive Therapy for Children With Microcephaly, Hyperkinetic Movements, or Global Developmental Delay
NCT05322980	Not specified	COMPLETED	Summary of Infants Weighing 500 Grams or Less
NCT06019182	Not specified	RECRUITING	MEHMO Natural History and Biomarkers
NCT06566066	Not specified	RECRUITING	Register for Patients With Thyroid Hormone Resistance.
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns