POP1

Summary

POP1 (POP1 ribonuclease P/MRP subunit, HGNC:30129) is a protein-coding gene on chromosome 8q22.2, encoding Ribonucleases P/MRP protein subunit POP1 (Q99575). Component of ribonuclease P, a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5’-ends.

This gene encodes the protein subunit of two different small nucleolar ribonucleoprotein complexes: the endoribonuclease for mitochondrial RNA processing complex and the ribonuclease P complex. The encoded protein is a ribonuclease that localizes to the nucleus and functions in pre-RNA processing. This protein is also an autoantigen in patients suffering from connective tissue diseases. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 10940 — RefSeq curated summary.

At a glance

• Gene–disease (curated): anauxetic dysplasia 2 (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 504 total — 24 pathogenic, 6 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001145860

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30129
Approved symbol	POP1
Name	POP1 ribonuclease P/MRP subunit
Location	8q22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000104356
Ensembl biotype	protein_coding
OMIM	602486
Entrez	10940

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 retained_intron

ENST00000349693, ENST00000401707, ENST00000517435, ENST00000522319, ENST00000884875, ENST00000884876, ENST00000884877, ENST00000916451, ENST00000916452, ENST00000916453

RefSeq mRNA: 3 — MANE Select: NM_001145860 NM_001145860, NM_001145861, NM_015029

CCDS: CCDS6277

Canonical transcript exons

ENST00000401707 — 16 exons

Exon	Start	End
ENSE00000701556	98148815	98149006
ENSE00000701560	98150485	98150639
ENSE00000701561	98156050	98156412
ENSE00000888403	98146568	98146683
ENSE00000905570	98127595	98127762
ENSE00000905571	98128365	98128540
ENSE00000905572	98129978	98130226
ENSE00000905573	98133949	98134036
ENSE00000905574	98134472	98134659
ENSE00000905575	98136482	98136738
ENSE00000905576	98136861	98136954
ENSE00000905577	98140078	98140189
ENSE00000905578	98140769	98140888
ENSE00001370963	98123336	98123479
ENSE00001553933	98117293	98117390
ENSE00002104487	98157617	98159835

Expression profiles

Bgee: expression breadth ubiquitous, 179 present calls, max score 85.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.1646 / max 185.9860, expressed in 1759 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89931	11.7397	1758
89932	0.4249	200

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.12	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.22	gold quality
cortical plate	UBERON:0005343	76.24	gold quality
stromal cell of endometrium	CL:0002255	75.48	gold quality
ganglionic eminence	UBERON:0004023	75.17	gold quality
ventricular zone	UBERON:0003053	74.86	gold quality
adrenal tissue	UBERON:0018303	74.23	gold quality
islet of Langerhans	UBERON:0000006	73.75	gold quality
calcaneal tendon	UBERON:0003701	73.20	gold quality
apex of heart	UBERON:0002098	72.79	gold quality
granulocyte	CL:0000094	70.56	gold quality
rectum	UBERON:0001052	70.49	gold quality
cerebellar cortex	UBERON:0002129	70.19	gold quality
cerebellar hemisphere	UBERON:0002245	70.19	gold quality
esophagus mucosa	UBERON:0002469	69.70	gold quality
right hemisphere of cerebellum	UBERON:0014890	69.67	gold quality
mucosa of transverse colon	UBERON:0004991	69.59	gold quality
leukocyte	CL:0000738	68.98	gold quality
right ovary	UBERON:0002118	68.91	gold quality
cerebellum	UBERON:0002037	68.89	gold quality
monocyte	CL:0000576	68.72	gold quality
right adrenal gland cortex	UBERON:0035827	68.57	gold quality
mononuclear cell	CL:0000842	68.54	gold quality
pancreatic ductal cell	CL:0002079	67.95	silver quality
muscle of leg	UBERON:0001383	67.89	gold quality
gastrocnemius	UBERON:0001388	67.88	gold quality
descending thoracic aorta	UBERON:0002345	67.80	gold quality
right adrenal gland	UBERON:0001233	67.79	gold quality
esophagus	UBERON:0001043	67.61	gold quality
pancreas	UBERON:0001264	67.58	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

71 targeting POP1, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-3659	99.70	67.97	694
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-4804-3P	99.65	67.78	866

Literature-anchored findings (GeneRIF, showing 13)

• A transient association of protein subunits may be inversely correlated to its involvement in pre-rRNA processing. (PMID:16723659)
• Data idenified two cleavage sites for RNase MRP/RNase P in the coding sequence of viperin mRNA. (PMID:21053045)
• POP1 gene expression is increased in classic variant of papillary thyroid carcinoma. (PMID:21509594)
• Mitochondrial ribonuclease P structure provides insight into the evolution of catalytic strategies for precursor-trna 5’ processing. (PMID:22991464)
• S-palmitoylation alters conformation or secondary structure of Trx1, as well as decreases the ability of Trx1 to transfer electrons from thioredoxin reductase to S-nitrosylated protein-tyrosine phosphatase 1B and S-nitroso-glutathione (PMID:25839653)
• by inhibiting inflammasome assembly, provides a regulatory feedback loop that shuts down excessive inflammatory responses; Cryopyrin-Associated Periodic Syndrome patients exhibit reduced expression (PMID:26275995)
• we reported the third case with POP1-related AAD. This phenotype may appropriately be termed AAD type 2. (PMID:27380734)
• Biallelic POP1 mutations were identified in both. A missense mutation and a novel single base deletion were detected in proband 1, p.[Pro582Ser]:[Glu870fs*5]. Markedly reduced abundance of RMRP and elevated levels of pre5.8s rRNA was observed. In proband 2, a homozygous novel POP1 mutation was identified (PMID:28067412)
• The novel R211Q POP1 homozygous mutation causes different pathogenesis and skeletal changes from those of previously reported POP1-associated anauxetic dysplasia. (PMID:32134183)
• Clinical significance for diagnosis and prognosis of POP1 and its potential role in breast cancer: a comprehensive analysis based on multiple databases. (PMID:36084948)
• POP1 inhibits MSU-induced inflammasome activation and ameliorates gout. (PMID:36225929)
• POP1 promotes the progression of breast cancer through maintaining telomere integrity. (PMID:37010429)
• PGC-1alpha inhibits NLRP3 signaling through transcriptional activation of POP1 to alleviate inflammation and strengthen osteogenic differentiation of lipopolysaccharide-induced human periodontal stem cells. (PMID:38763227)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pop1	ENSDARG00000102087
mus_musculus	Pop1	ENSMUSG00000022325
rattus_norvegicus	Pop1	ENSRNOG00000005243
drosophila_melanogaster	Pop1	FBGN0026702
caenorhabditis_elegans		WBGENE00015486

Paralogs (1): SERAC1 (ENSG00000122335)

Protein

Protein identifiers

Ribonucleases P/MRP protein subunit POP1 — Q99575 (reviewed: Q99575)

All UniProt accessions (2): Q99575, E5RK39

UniProt curated annotations — full annotation on UniProt →

Function. Component of ribonuclease P, a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5’-ends. Also a component of the MRP ribonuclease complex, which cleaves pre-rRNA sequences.

Subunit / interactions. Component of nuclear RNase P and RNase MRP ribonucleoproteins. RNase P consists of a catalytic RNA moiety and 10 different protein chains; POP1, POP4, POP5, POP7, RPP14, RPP21, RPP25, RPP30, RPP38 and RPP40. Within the RNase P complex, POP1, POP7 and RPP25 form the ‘finger’ subcomplex, POP5, RPP14, RPP40 and homodimeric RPP30 form the ‘palm’ subcomplex, and RPP21, POP4 and RPP38 form the ‘wrist’ subcomplex. All subunits of the RNase P complex interact with the catalytic RNA. Several subunits of RNase P are also part of the RNase MRP complex. RNase MRP consists of a catalytic RNA moiety and about 8 protein subunits; POP1, POP7, RPP25, RPP30, RPP38, RPP40 and possibly also POP4 and POP5.

Subcellular location. Nucleus. Nucleolus.

Disease relevance. Anauxetic dysplasia 2 (ANXD2) [MIM:617396] An autosomal recessive spondyloepimetaphyseal dysplasia characterized by severe short stature of prenatal onset, very short adult height (less than 1 meter), hypodontia, midface hypoplasia, and mild intellectual disability. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (3): NP_001139332, NP_001139333, NP_055844 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009723	Pop1_N	Domain
IPR012590	POPLD_dom	Domain
IPR039182	Pop1	Family
IPR055079	POP1_C	Domain

Pfam: PF06978, PF08170, PF22770

Enzyme classification (BRENDA):

• EC 3.1.26.5 — ribonuclease P (BRENDA: 188 organisms, 407 substrates, 80 inhibitors, 54 Km, 43 kcat entries)

Substrate kinetics (BRENDA)

24 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
HUMAN PRE-TRNATYR	0.0001–0.0005	5
PRE-TRNATYR	—	5
PRE-TRNAASP	—	4
PTRNATYR	0.0002–0.0305	4
TRNA PRECURSOR	—	4
PRE-TRNA-TYR	0.0001	2
PRE-TRNATHR(AGT)	0.0035–0.05	2
RNASE P RIBOSWITCH A	0.0064–0.0081	2
TRNAPHE (G+1) PRECURSOR	—	2
TRNATYR	—	2
PMINI3PBUG	0.0013	1
PRE-TRNA	—	1
PRE-TRNA SUPS1 TRNASER	0.0002	1
PRE-TRNA-ASP	0.0003	1
PRE-TRNA-CYS	0.0006	1

UniProt features (24 total): sequence variant 8, region of interest 6, compositionally biased region 5, modified residue 4, chain 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
9UH7	ELECTRON MICROSCOPY	2.84
9UH9	ELECTRON MICROSCOPY	3.47
6AHU	ELECTRON MICROSCOPY	3.66
6AHR	ELECTRON MICROSCOPY	3.92
9UHA	ELECTRON MICROSCOPY	3.93

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99575-F1	74.77	0.47

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 (4): 367, 584, 729, 730

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6784531	tRNA processing in the nucleus

MSigDB gene sets: 231 (showing top): GOMF_ENDONUCLEASE_ACTIVITY, GOMF_RNA_NUCLEASE_ACTIVITY, GOMF_NUCLEASE_ACTIVITY, GOBP_TRNA_METABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, WEI_MYCN_TARGETS_WITH_E_BOX, MUELLER_PLURINET, GOMF_RNA_ENDONUCLEASE_ACTIVITY, NIKOLSKY_BREAST_CANCER_8Q12_Q22_AMPLICON, chr8q22, DODD_NASOPHARYNGEAL_CARCINOMA_UP, KAYO_AGING_MUSCLE_UP, GOBP_TRNA_PROCESSING, REACTOME_METABOLISM_OF_RNA

GO Biological Process (3): tRNA 5’-leader removal (GO:0001682), tRNA processing (GO:0008033), tRNA decay (GO:0016078)

GO Molecular Function (4): RNA binding (GO:0003723), ribonuclease P RNA binding (GO:0033204), ribonuclease P activity (GO:0004526), protein binding (GO:0005515)

GO Cellular Component (7): ribonuclease MRP complex (GO:0000172), obsolete extracellular space (GO:0005615), nucleoplasm (GO:0005654), nucleolar ribonuclease P complex (GO:0005655), nucleolus (GO:0005730), multimeric ribonuclease P complex (GO:0030681), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
tRNA processing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
tRNA metabolic process	2
nuclear lumen	2
tRNA 5’-end processing	1
RNA processing	1
RNA catabolic process	1
nucleic acid binding	1
RNA binding	1
tRNA-specific ribonuclease activity	1
RNA endonuclease activity producing 5’-phosphomonoesters, hydrolytic mechanism	1
binding	1
sno(s)RNA-containing ribonucleoprotein complex	1
endoribonuclease complex	1
cellular anatomical structure	1
nucleolus	1
multimeric ribonuclease P complex	1
nuclear protein-containing complex	1
intracellular membraneless organelle	1
ribonuclease P complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1036 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POP1	POP4	O95707	667
POP1	RPP25	Q9BUL9	638
POP1	RPP30	P78346	578
POP1	POP5	Q969H6	544
POP1	TLCD1	Q96CP7	480
POP1	RPP40	O75818	479
POP1	ZNF623	O75123	479
POP1	MTRNR2L3	P0CJ70	479
POP1	RPP38	P78345	479
POP1	ZHX1-C8orf76	Q96EF9	475
POP1	EFCAB8	A8MWE9	463
POP1	C8orf76	Q96K31	448
POP1	PYCR3	Q53H96	447
POP1	TIGD5	Q53EQ6	447
POP1	C8orf33	Q9H7E9	431

IntAct

217 interactions, top by confidence:

A	B	Type	Score
RPP25	POP7	psi-mi:“MI:0914”(association)	0.810
POP1	POP4	psi-mi:“MI:0915”(physical association)	0.740
RPP30	POP7	psi-mi:“MI:0914”(association)	0.730
POP1	RPP25	psi-mi:“MI:0915”(physical association)	0.670
RPP14	RPP40	psi-mi:“MI:0914”(association)	0.670
C18orf21	POP7	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
POP4	POP7	psi-mi:“MI:0914”(association)	0.640
NPM1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.610
POP1	POP5	psi-mi:“MI:0915”(physical association)	0.560
NP	KPNA6	psi-mi:“MI:0914”(association)	0.550
RRP8	NVL	psi-mi:“MI:0914”(association)	0.530
PRR11	NVL	psi-mi:“MI:0914”(association)	0.530
ZNF71	NVL	psi-mi:“MI:0914”(association)	0.530
RPL7	ZBTB24	psi-mi:“MI:0914”(association)	0.530
POP4	NME2P1	psi-mi:“MI:0914”(association)	0.530
RPP21	POP7	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
RBM4	NVL	psi-mi:“MI:0914”(association)	0.530
POP7	RPP40	psi-mi:“MI:0914”(association)	0.530
RPP25L	RPP40	psi-mi:“MI:0914”(association)	0.530
C18orf21	RPP40	psi-mi:“MI:0914”(association)	0.530
NIFK	RSL1D1	psi-mi:“MI:0914”(association)	0.530
RPP30	RPP38	psi-mi:“MI:0914”(association)	0.530
MAGEB2	GTPBP10	psi-mi:“MI:0914”(association)	0.530

BioGRID (367): POP1 (Affinity Capture-MS), POP1 (Affinity Capture-MS), POP1 (Affinity Capture-MS), POP1 (Affinity Capture-MS), POP1 (Affinity Capture-MS), POP1 (Affinity Capture-MS), POP1 (Affinity Capture-MS), POP1 (Affinity Capture-MS), POP1 (Affinity Capture-MS), POP1 (Affinity Capture-MS), POP1 (Affinity Capture-MS), POP1 (Affinity Capture-MS), G3BP1 (Co-fractionation), POP1 (Co-fractionation), SF3A3 (Co-fractionation)

ESM2 similar proteins: A7LFZ6, B5X561, B8BDK0, C8KI33, D0EL35, F4HZK4, F4I443, F4I7C7, F4IDY5, F4IL30, F4JNY0, F4K2M8, F4K3G5, F4KIX0, K7TQE3, O22199, O22267, O65573, P84634, Q0IY07, Q0J0B2, Q0P4D6, Q0WUR5, Q14AW5, Q2TSC7, Q56XZ1, Q5SNL7, Q5W9E7, Q5XVJ4, Q6AUQ7, Q6E7H0, Q7XD96, Q84RK2, Q8H111, Q8VZA0, Q8W489, Q93YN9, Q99575, Q9C5Q8, Q9C5S2

Diamond homologs: P41812, Q99575, F4IL30, Q11188

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
POP1	“form complex”	“Ribonuclease MRP complex”	binding
POP1	“form complex”	“Nucleolar ribonuclease P complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 200 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
tRNA processing	7	19.8×	1e-06
Peptide chain elongation	19	19.1×	2e-17
Viral mRNA Translation	19	19.1×	2e-17
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	19	18.9×	2e-17
Selenocysteine synthesis	19	18.1×	3e-17
Eukaryotic Translation Termination	19	18.1×	3e-17
rRNA processing in the nucleus and cytosol	14	17.9×	9e-13
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	19	17.8×	3e-17

GO biological processes:

GO term	Partners	Fold	FDR
regulation of mRNA splicing, via spliceosome	5	26.2×	1e-04
cytoplasmic translation	21	23.0×	4e-20
ribosomal large subunit biogenesis	7	18.4×	1e-05
rRNA processing	19	15.9×	2e-15
ribosomal small subunit biogenesis	10	13.5×	6e-07
translation	22	13.4×	3e-16
regulation of alternative mRNA splicing, via spliceosome	9	13.0×	5e-06
negative regulation of translation	9	10.4×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	24
Likely pathogenic	6
Uncertain significance	220
Likely benign	168
Benign	60

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1386533	NM_001145860.2(POP1):c.1801C>T (p.Gln601Ter)	Pathogenic
1433652	NM_001145860.2(POP1):c.935G>A (p.Trp312Ter)	Pathogenic
1443334	NC_000008.10:g.(?99146680)(99149202_?)del	Pathogenic
1496847	NM_001145860.2(POP1):c.2290G>T (p.Glu764Ter)	Pathogenic
1502765	NM_001145860.2(POP1):c.1531del (p.Asp511fs)	Pathogenic
1923089	NM_001145860.2(POP1):c.418C>T (p.Arg140Ter)	Pathogenic
1933405	NM_001145860.2(POP1):c.2254del (p.Thr752fs)	Pathogenic
1985811	NM_001145860.2(POP1):c.925dup (p.Thr309fs)	Pathogenic
2016061	NM_001145860.2(POP1):c.5C>G (p.Ser2Ter)	Pathogenic
2125742	NM_001145860.2(POP1):c.1909C>T (p.Arg637Ter)	Pathogenic
2216148	NM_001145860.2(POP1):c.1195dup (p.Ile399fs)	Pathogenic
2719888	NM_001145860.2(POP1):c.706C>T (p.Arg236Ter)	Pathogenic
2960960	NM_001145860.2(POP1):c.816del (p.Ile272fs)	Pathogenic
2969675	NM_001145860.2(POP1):c.2167G>T (p.Glu723Ter)	Pathogenic
3001580	NM_001145860.2(POP1):c.421C>T (p.Arg141Ter)	Pathogenic
3645545	NM_001145860.2(POP1):c.897del (p.Lys299fs)	Pathogenic
3722822	NM_001145860.2(POP1):c.1105G>T (p.Glu369Ter)	Pathogenic
393588	NM_001145860.2(POP1):c.1573C>T (p.Pro525Ser)	Pathogenic
417736	NM_001145860.2(POP1):c.1744C>T (p.Pro582Ser)	Pathogenic
417737	NM_001145860.2(POP1):c.2607del (p.Glu870fs)	Pathogenic
417738	NM_001145860.2(POP1):c.1531G>T (p.Asp511Tyr)	Pathogenic
4706120	NM_001145860.2(POP1):c.346del (p.Ser116fs)	Pathogenic
4711921	NM_001145860.2(POP1):c.1517del (p.Gly506fs)	Pathogenic
4734776	NM_001145860.2(POP1):c.513dup (p.Glu172fs)	Pathogenic
1332833	NM_001145860.2(POP1):c.2087T>A (p.Val696Asp)	Likely pathogenic
2770773	NM_001145860.2(POP1):c.1362+2T>G	Likely pathogenic
2975670	NM_001145860.2(POP1):c.311-2A>G	Likely pathogenic
3068111	NM_001145860.2(POP1):c.486+2T>C	Likely pathogenic
3604900	NM_001145860.2(POP1):c.823+1G>C	Likely pathogenic
3612147	NM_001145860.2(POP1):c.1710+1G>A	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

6686 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:98128386:G:C	R111P	0.998
8:98128388:G:C	A112P	0.998
8:98128480:A:C	R142S	0.998
8:98128480:A:T	R142S	0.998
8:98128377:C:A	A108D	0.997
8:98128479:G:C	R142T	0.997
8:98130110:T:A	W207R	0.997
8:98130110:T:C	W207R	0.997
8:98148956:T:A	W618R	0.997
8:98148956:T:C	W618R	0.997
8:98128415:G:C	A121P	0.996
8:98128482:C:A	A143D	0.996
8:98128506:T:C	L151P	0.996
8:98128382:G:C	A110P	0.995
8:98128391:G:C	A113P	0.995
8:98128395:A:T	E114V	0.994
8:98128403:G:C	A117P	0.994
8:98128473:G:C	R140P	0.994
8:98128476:G:C	R141P	0.994
8:98128502:C:A	R150S	0.994
8:98130125:T:C	F212L	0.994
8:98130127:T:A	F212L	0.994
8:98130127:T:G	F212L	0.994
8:98148995:T:A	W631R	0.994
8:98148995:T:C	W631R	0.994
8:98128481:G:C	A143P	0.993
8:98128487:A:C	S145R	0.993
8:98128489:C:A	S145R	0.993
8:98128489:C:G	S145R	0.993
8:98130076:A:C	R195S	0.993

dbSNP variants (sampled 300 via entrez): RS1000031327 (8:98149738 A>G), RS1000058645 (8:98135416 A>G), RS1000105245 (8:98142754 A>G), RS1000119741 (8:98155754 T>C), RS1000277098 (8:98155473 G>C), RS1000304193 (8:98136217 A>G,T), RS1000344019 (8:98118097 C>T), RS1000381129 (8:98129783 G>A), RS1000453472 (8:98154381 C>T), RS1000531711 (8:98124698 A>C), RS1000676032 (8:98116743 C>A,G), RS1000677325 (8:98160231 T>C), RS1000707694 (8:98131230 A>G), RS1001017629 (8:98118630 T>C), RS1001085737 (8:98136455 A>G,T)

Disease associations

OMIM: gene MIM:602486 | disease phenotypes: MIM:617396

GenCC curated gene-disease

Disease	Classification	Inheritance
anauxetic dysplasia 2	Definitive	Autosomal recessive
anauxetic dysplasia	Supportive	Autosomal recessive

Mondo (2): anauxetic dysplasia 2 (MONDO:0054561), anauxetic dysplasia (MONDO:0011773)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST011998_5	Glucocorticoid receptor gene expression in B-cell precursor acute lymphoblastic leukaemia	3.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C538256	Anauxetic dysplasia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066401 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.28	Kd	52.73	nM	CHEMBL5653589
7.28	ED50	52.73	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149036: Binding affinity to human POP1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0527	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression, affects cotreatment, increases abundance, increases expression	6
Air Pollutants	increases abundance, increases oxidation, decreases expression, affects cotreatment	3
bisphenol S	affects expression, affects cotreatment, decreases expression	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Tunicamycin	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
afuresertib	decreases expression	1
FR900359	affects phosphorylation	1
alpha phellandrene	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	affects cotreatment, decreases expression	1
sodium arsenate	decreases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
coumarin	increases phosphorylation	1
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	affects expression	1
abrine	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
CHEMBL5652078	Binding	Binding affinity to human POP1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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