KREMEN1

Summary

KREMEN1 (kringle containing transmembrane protein 1, HGNC:17550) is a protein-coding gene on chromosome 22q12.1, encoding Kremen protein 1 (Q96MU8). Receptor for Dickkopf proteins.

This gene encodes a high-affinity dickkopf homolog 1 (DKK1) transmembrane receptor that functionally cooperates with DKK1 to block wingless (WNT)/beta-catenin signaling. The encoded protein is a component of a membrane complex that modulates canonical WNT signaling through lipoprotein receptor-related protein 6 (LRP6). It contains extracellular kringle, WSC, and CUB domains. Mutations in this gene result in ectodermal dysplasia. This protein has also been found to be a functional receptor for Coxsackievirus A10 and may be an alternative entry receptor for SARS-CoV-2.

Source: NCBI Gene 83999 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ectodermal dysplasia 13, hair/tooth type (Strong, GenCC)
• GWAS associations: 39
• Clinical variants (ClinVar): 136 total — 3 pathogenic
• Phenotypes (HPO): 12
• MANE Select transcript: NM_001039570

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17550
Approved symbol	KREMEN1
Name	kringle containing transmembrane protein 1
Location	22q12.1
Locus type	gene with protein product
Status	Approved
Aliases	KRM1
Ensembl gene	ENSG00000183762
Ensembl biotype	protein_coding
OMIM	609898
Entrez	83999

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 11 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000327813, ENST00000400335, ENST00000407188, ENST00000453585, ENST00000474001, ENST00000479755, ENST00000863394, ENST00000863395, ENST00000863396, ENST00000863397, ENST00000863398, ENST00000943419, ENST00000943421, ENST00000943422

RefSeq mRNA: 2 — MANE Select: NM_001039570 NM_001039570, NM_032045

CCDS: CCDS13849, CCDS43000

Canonical transcript exons

ENST00000400335 — 9 exons

Exon	Start	End
ENSE00001292367	29121357	29121481
ENSE00001305029	29140282	29140366
ENSE00001306074	29094258	29094420
ENSE00001326512	29125263	29125416
ENSE00001330732	29098862	29098953
ENSE00001542409	29138624	29138782
ENSE00001846200	29141944	29146820
ENSE00001868507	29073035	29073227
ENSE00003549742	29137342	29137674

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 94.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.0767 / max 231.0895, expressed in 1561 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191592	7.4842	1540
191593	1.3418	384
191591	0.2507	110

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	94.57	gold quality
decidua	UBERON:0002450	93.96	gold quality
parotid gland	UBERON:0001831	93.12	gold quality
lower esophagus mucosa	UBERON:0035834	92.15	gold quality
cardiac muscle of right atrium	UBERON:0003379	92.09	silver quality
vena cava	UBERON:0004087	91.53	gold quality
tibialis anterior	UBERON:0001385	91.18	gold quality
left ventricle myocardium	UBERON:0006566	90.80	silver quality
gingival epithelium	UBERON:0001949	90.66	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.36	gold quality
esophagus mucosa	UBERON:0002469	90.04	gold quality
gingiva	UBERON:0001828	88.76	gold quality
body of tongue	UBERON:0011876	88.65	gold quality
myocardium	UBERON:0002349	88.07	silver quality
skeletal muscle tissue	UBERON:0001134	87.96	gold quality
quadriceps femoris	UBERON:0001377	87.91	gold quality
skin of abdomen	UBERON:0001416	87.60	gold quality
vastus lateralis	UBERON:0001379	87.53	silver quality
kidney epithelium	UBERON:0004819	87.46	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	87.33	gold quality
muscle tissue	UBERON:0002385	87.26	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.18	gold quality
cardiac atrium	UBERON:0002081	87.13	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.02	gold quality
right atrium auricular region	UBERON:0006631	86.92	gold quality
apex of heart	UBERON:0002098	86.72	gold quality
epithelium of nasopharynx	UBERON:0001951	86.67	gold quality
skin of leg	UBERON:0001511	86.64	gold quality
pons	UBERON:0000988	86.63	gold quality
cardia of stomach	UBERON:0001162	86.58	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.84
E-MTAB-7303	no	115.08

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI1

miRNA regulators (miRDB)

200 targeting KREMEN1, 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-1277-5P	100.00	73.95	5056
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4715-3P	99.98	66.03	670
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-LET-7D-5P	99.96	71.76	1632

Literature-anchored findings (GeneRIF, showing 17)

• Functional characterization of related Kremen proteins in mouse. (PMID:12050670)
• Kremen may not be essential for Dkk1-mediated Wnt antagonism and Kremen may only play a role when cells express a high level of LRP5/6 (PMID:18502762)
• This study demonstrated that a representative tSNP of KREMEN1 might modulate the risk of schizophrenia in the Japanese population. (PMID:20153141)
• The mRNA expression levels of DKK-1 binding receptor LRP5/6 and Krm1/2 in SCs from patients with MM were significantly higher than those in myeloma cells and in SCs from healthy donors. (PMID:20846389)
• Six Dkk-1, three Sost, one Kremen-1 and 10 LRP-5 polymorphisms were significantly associated with radiological progression of rheumatoid arthritis joint destruction. (PMID:23041840)
• Kremen1 has a pro-apoptotic activity that is decreased upon Dkk1 binding or by cancer mutations. (PMID:26206087)
• Ectodermal dysplasia including oligodontia is due to homozygosity for KREMEN1 p.F209S (c.626 T>C). (PMID:27049303)
• Structure of the dual-mode Wnt regulator Kremen1 and insight into ternary complex formation with LRP6 and DKK1 have been presented. (PMID:27524201)
• Thai family study that has identified the second and third mutations found in KREMEN1 confirms that KREMEN1 is a human disease gene for autosomal recessive ectodermal dysplasia 13, hair/tooth type. Agenesis of permanent maxillary lateral incisors and mandibular anterior teeth could be a unique manifestation of KREMEN1 mutations. (PMID:29526031)
• Dkk4 CRD2 mediates high-affinity binding to both the E1E2 region of low-density lipoprotein receptor-related protein 6 (LRP6 E1E2) and the Kremen1 (Krm1) extracellular domain. (PMID:29925589)
• MiR-137 repressed KREMEN1 expression in neuronal cells. (PMID:31447119)
• CV-A10 mature virus alone and in complex with KRM1 as well as of the CV-A10 A-particle. (PMID:31911601)
• Replication of 15 loci involved in human plasma protein N-glycosylation in 4802 samples from four cohorts. (PMID:32521004)
• Molecular basis of Coxsackievirus A10 entry using the two-in-one attachment and uncoating receptor KRM1. (PMID:32690697)
• Novel homozygous KREMEN1 mutation causes ectodermal dysplasia. (PMID:34028942)
• Receptome profiling identifies KREMEN1 and ASGR1 as alternative functional receptors of SARS-CoV-2. (PMID:34837059)
• Novel SARS-CoV-2 receptors: ASGR1 and KREMEN1. (PMID:34903854)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	kremen1	ENSDARG00000062579
mus_musculus	Kremen1	ENSMUSG00000020393
rattus_norvegicus	Kremen1	ENSRNOG00000051487

Paralogs (1): KREMEN2 (ENSG00000131650)

Protein

Protein identifiers

Kremen protein 1 — Q96MU8 (reviewed: Q96MU8)

Alternative names: Dickkopf receptor, Kringle domain-containing transmembrane protein 1, Kringle-containing protein marking the eye and the nose

All UniProt accessions (2): H7BZ87, Q96MU8

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for Dickkopf proteins. Cooperates with DKK1/2 to inhibit Wnt/beta-catenin signaling by promoting the endocytosis of Wnt receptors LRP5 and LRP6. In the absence of DKK1, potentiates Wnt-beta-catenin signaling by maintaining LRP5 or LRP6 at the cell membrane. Can trigger apoptosis in a Wnt-independent manner and this apoptotic activity is inhibited upon binding of the ligand DKK1. Plays a role in limb development; attenuates Wnt signaling in the developing limb to allow normal limb patterning and can also negatively regulate bone formation. Modulates cell fate decisions in the developing cochlea with an inhibitory role in hair cell fate specification.

Subunit / interactions. Forms a ternary complex with DKK1 and LRP6. Interacts with LRP6 in a DKK1-dependent manner. Interacts with DKK1 and RSPO1 (via FU repeats).

Subcellular location. Cell membrane.

Disease relevance. Ectodermal dysplasia 13, hair/tooth type (ECTD13) [MIM:617392] A form of ectodermal dysplasia, a disorder due to abnormal development of two or more ectodermal structures. ECTD13 is an autosomal recessive form characterized by severe oligodontia accompanied by anomalies of hair and skin. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Exon 1 splicing donor site is not canonical.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96MU8-1	1	yes
Q96MU8-2	2
Q96MU8-3	3

RefSeq proteins (2): NP_001034659, NP_114434 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000001	Kringle	Domain
IPR000859	CUB_dom	Domain
IPR002889	WSC_carb-bd	Domain
IPR013806	Kringle-like	Homologous_superfamily
IPR017076	Kremen	Family
IPR018056	Kringle_CS	Conserved_site
IPR035914	Sperma_CUB_dom_sf	Homologous_superfamily
IPR038178	Kringle_sf	Homologous_superfamily
IPR051836	Kremen_rcpt	Family

Pfam: PF00051, PF00431, PF01822

UniProt features (63 total): strand 24, disulfide bond 8, turn 8, glycosylation site 6, splice variant 3, helix 3, domain 3, topological domain 2, signal peptide 1, chain 1, sequence variant 1, sequence conflict 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
5FWS	X-RAY DIFFRACTION	1.9
5FWT	X-RAY DIFFRACTION	2.1
9VFR	ELECTRON MICROSCOPY	2.55
5FWU	X-RAY DIFFRACTION	2.8
7BZT	ELECTRON MICROSCOPY	3
7BZU	ELECTRON MICROSCOPY	3
5FWV	X-RAY DIFFRACTION	3.2
5FWW	X-RAY DIFFRACTION	3.5
6SNW	ELECTRON MICROSCOPY	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96MU8-F1	79.43	0.64

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 (8): 32–114, 55–95, 84–109, 122–186, 147–167, 151–169, 190–198, 214–240

Glycosylation sites (6): 59, 217, 293, 333, 345, 45

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-201681	TCF dependent signaling in response to WNT
R-HSA-3772470	Negative regulation of TCF-dependent signaling by WNT ligand antagonists
R-HSA-5339717	Signaling by LRP5 mutants
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-195721	Signaling by WNT
R-HSA-4791275	Signaling by WNT in cancer
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers

MSigDB gene sets: 217 (showing top): GOBP_REGENERATION, GOBP_NEUROGENESIS, GOBP_RESPONSE_TO_AXON_INJURY, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GGGTGGRR_PAX4_03, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, FOSTER_TOLERANT_MACROPHAGE_UP, GOBP_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_REGULATION_OF_RESPONSE_TO_WOUNDING, GOBP_APPENDAGE_DEVELOPMENT, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, GOBP_REGULATION_OF_NEURON_PROJECTION_REGENERATION

GO Biological Process (9): apoptotic process (GO:0006915), cell communication (GO:0007154), signal transduction (GO:0007165), Wnt signaling pathway (GO:0016055), negative regulation of ossification (GO:0030279), negative regulation of axon regeneration (GO:0048681), limb development (GO:0060173), regulation of canonical Wnt signaling pathway (GO:0060828), negative regulation of canonical Wnt signaling pathway (GO:0090090)

GO Molecular Function (2): transmembrane signaling receptor activity (GO:0004888), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), membrane (GO:0016020), neuronal cell body (GO:0043025)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Signaling by WNT	1
TCF dependent signaling in response to WNT	1
Signaling by WNT in cancer	1
Signal Transduction	1
Diseases of signal transduction by growth factor receptors and second messengers	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	2
canonical Wnt signaling pathway	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell surface receptor signaling pathway	1
ossification	1
regulation of ossification	1
negative regulation of multicellular organismal process	1
axon regeneration	1
negative regulation of response to external stimulus	1
regulation of axon regeneration	1
negative regulation of neuron projection regeneration	1
negative regulation of response to wounding	1
appendage development	1
regulation of Wnt signaling pathway	1
negative regulation of Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
signaling receptor activity	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1
somatodendritic compartment	1
cell body	1

Protein interactions and networks

STRING

1052 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KREMEN1	DKK1	O94907	999
KREMEN1	DKK2	Q9UBU2	984
KREMEN1	LRP5	O75197	982
KREMEN1	DKK4	Q9UBT3	945
KREMEN1	LRP6	O75581	848
KREMEN1	DKK3	Q9UBP4	754
KREMEN1	WNT1	P04628	721
KREMEN1	CTNNB1	P35222	714
KREMEN1	ASGR1	P07306	649
KREMEN1	RSPO1	Q2MKA7	642
KREMEN1	WIF1	Q9Y5W5	606
KREMEN1	FRZB	Q92765	567
KREMEN1	ZNRF3	Q9ULT6	566
KREMEN1	KREMEN2	Q8NCW0	534
KREMEN1	TMPRSS2	O15393	459

IntAct

7 interactions, top by confidence:

A	B	Type	Score
DKK1	LRP6	psi-mi:“MI:0915”(physical association)	0.960
KREMEN1	DKK1	psi-mi:“MI:0915”(physical association)	0.670
KREMEN1	DKK1	psi-mi:“MI:0407”(direct interaction)	0.670
LRP6	KREMEN1	psi-mi:“MI:0407”(direct interaction)	0.440
Lrp6	KREMEN1	psi-mi:“MI:0915”(physical association)	0.400
KREMEN1	PCNA	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (2): S (Reconstituted Complex), S (Affinity Capture-Western)

ESM2 similar proteins: A0JNA2, A4FUY1, C0HL12, O14514, O19131, O60241, O75325, P0C5H6, P15151, P32506, P32507, P70225, P98095, Q05BQ1, Q13477, Q14626, Q14CZ8, Q29RN8, Q3UHD1, Q4V9Z5, Q53EL9, Q5DRQ8, Q5R7Y0, Q5RF19, Q5STE3, Q63148, Q64385, Q6AX42, Q6BAA4, Q6MZW2, Q6UWL2, Q6UWL6, Q6UXD5, Q6WN34, Q7TSK2, Q7TSU7, Q8BHA1, Q8BQC3, Q8CGM1, Q8IVU1

Diamond homologs: A2YPX3, D4AUF4, P84675, Q0D3N0, Q505J3, Q5QQ53, Q658N2, Q7KVA1, Q80XH4, Q8GY91, Q8K1S7, Q8NCW0, Q924S4, Q96MU8, Q99N43, Q9FLC0, D3ZTE0, O18783, P00734, P00735, P00747, P00749, P00750, P04185, P06867, P06868, P06869, P08519, P11214, P12545, P14210, P15638, P16227, P17945, P18292, P19221, P19637, P20918, P26927, P26928

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
DKK1	up-regulates	KREMEN1	binding
KREMEN1	up-regulates	LRP6

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	83
Likely benign	24
Benign	13

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1076756	NC_000022.10:g.(?29105984)(30337586_?)del	Pathogenic
2310909	NM_001039570.3(KREMEN1):c.357del (p.Gly120fs)	Pathogenic
393469	NM_001039570.3(KREMEN1):c.626T>C (p.Phe209Ser)	Pathogenic

SpliceAI

2184 predictions. Top by Δscore:

Variant	Effect	Δscore
22:29094257:GA:G	acceptor_gain	1.0000
22:29094257:GAGT:G	acceptor_gain	1.0000
22:29098925:G:GT	donor_gain	1.0000
22:29098952:GA:G	donor_gain	1.0000
22:29098954:G:GG	donor_gain	1.0000
22:29137670:CCAAG:C	donor_gain	1.0000
22:29137672:AAG:A	donor_gain	1.0000
22:29137672:AAGG:A	donor_loss	1.0000
22:29137673:AG:A	donor_gain	1.0000
22:29137673:AGGTA:A	donor_loss	1.0000
22:29137674:GG:G	donor_gain	1.0000
22:29137675:G:GG	donor_gain	1.0000
22:29137675:GTA:G	donor_loss	1.0000
22:29138621:CAGCC:C	acceptor_loss	1.0000
22:29138622:A:AG	acceptor_gain	1.0000
22:29138622:AGCC:A	acceptor_gain	1.0000
22:29138623:G:GA	acceptor_gain	1.0000
22:29138623:GCC:G	acceptor_gain	1.0000
22:29138623:GCCG:G	acceptor_gain	1.0000
22:29138623:GCCGT:G	acceptor_gain	1.0000
22:29140367:G:GG	donor_gain	1.0000
22:29094252:TTCTA:T	acceptor_loss	0.9900
22:29094255:TAGA:T	acceptor_gain	0.9900
22:29094255:TAGAG:T	acceptor_loss	0.9900
22:29094256:A:AG	acceptor_gain	0.9900
22:29094257:G:GG	acceptor_gain	0.9900
22:29094257:G:T	acceptor_loss	0.9900
22:29094419:AGGTA:A	donor_loss	0.9900
22:29094420:GGTA:G	donor_loss	0.9900
22:29094421:G:C	donor_loss	0.9900

AlphaMissense

3004 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:29094340:G:C	W58C	1.000
22:29094340:G:T	W58C	1.000
22:29094416:T:A	C84S	0.999
22:29094417:G:C	C84S	0.999
22:29098889:G:C	W94C	0.999
22:29098889:G:T	W94C	0.999
22:29098890:T:A	C95S	0.999
22:29098891:G:C	C95S	0.999
22:29098925:G:C	W106C	0.999
22:29098925:G:T	W106C	0.999
22:29125359:T:C	C190R	0.999
22:29137657:T:C	F314S	0.999
22:29137668:T:G	Y318D	0.999
22:29094329:T:A	C55S	0.998
22:29094329:T:C	C55R	0.998
22:29094330:G:C	C55S	0.998
22:29094331:T:G	C55W	0.998
22:29094338:T:A	W58R	0.998
22:29094338:T:C	W58R	0.998
22:29094416:T:C	C84R	0.998
22:29094417:G:A	C84Y	0.998
22:29094418:C:G	C84W	0.998
22:29098890:T:C	C95R	0.998
22:29098892:C:G	C95W	0.998
22:29098933:G:A	C109Y	0.998
22:29121449:T:C	C147R	0.998
22:29121450:G:A	C147Y	0.998
22:29121451:C:G	C147W	0.998
22:29121461:T:C	C151R	0.998
22:29121462:G:A	C151Y	0.998

dbSNP variants (sampled 300 via entrez): RS1000012115 (22:29154357 A>C), RS1000035348 (22:29164524 G>A), RS1000044623 (22:29154107 T>C), RS1000059196 (22:29123510 A>G), RS1000077018 (22:29112426 T>G), RS1000274818 (22:29142700 A>C), RS1000304593 (22:29142365 T>C), RS1000325978 (22:29091726 A>G), RS1000414561 (22:29091514 A>C), RS1000433071 (22:29123841 G>A), RS1000467373 (22:29136614 C>T), RS1000503052 (22:29146653 A>C,T), RS1000528102 (22:29161120 A>G,T), RS1000577202 (22:29084948 G>T), RS1000604094 (22:29141260 CAT>C)

Disease associations

OMIM: gene MIM:609898 | disease phenotypes: MIM:114480, MIM:617392, MIM:614559

GenCC curated gene-disease

Disease	Classification	Inheritance
ectodermal dysplasia 13, hair/tooth type	Strong	Autosomal recessive

Mondo (3): hereditary breast carcinoma (MONDO:0016419), ectodermal dysplasia 13, hair/tooth type (MONDO:0044305), infantile cerebellar-retinal degeneration (MONDO:0013802)

Orphanet (2): Hereditary breast cancer (Orphanet:227535), Infantile cerebellar-retinal degeneration (Orphanet:313850)

HPO phenotypes

12 total (12 of 12 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000294	Low anterior hairline
HP:0000316	Hypertelorism
HP:0000431	Wide nasal bridge
HP:0000494	Downslanted palpebral fissures
HP:0000653	Sparse eyelashes
HP:0000677	Oligodontia
HP:0000968	Ectodermal dysplasia
HP:0002299	Brittle hair
HP:0005280	Depressed nasal bridge
HP:0012471	Thick vermilion border
HP:0045074	Thin eyebrow

GWAS associations

39 associations (top):

Study	Trait	p-value
GCST000829_15	Waist-hip ratio	1.000000e-11
GCST002553_2	Pancreatic cancer	1.000000e-08
GCST002782_199	Waist-to-hip ratio adjusted for body mass index	7.000000e-10
GCST002782_200	Waist-to-hip ratio adjusted for body mass index	2.000000e-06
GCST002782_201	Waist-to-hip ratio adjusted for body mass index	7.000000e-13
GCST002782_202	Waist-to-hip ratio adjusted for body mass index	7.000000e-06
GCST002782_203	Waist-to-hip ratio adjusted for body mass index	4.000000e-09
GCST002782_204	Waist-to-hip ratio adjusted for body mass index	6.000000e-12
GCST004064_41	Waist-hip ratio	1.000000e-08
GCST004064_78	Waist-hip ratio	1.000000e-09
GCST004505_5	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	8.000000e-09
GCST004505_6	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	3.000000e-06
GCST004567_111	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	6.000000e-09
GCST004567_125	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	1.000000e-13
GCST004567_133	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	2.000000e-06
GCST004567_16	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	8.000000e-09
GCST004567_34	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	1.000000e-13
GCST004567_52	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	2.000000e-06
GCST004576_60	Waist-to-hip ratio adjusted for body mass index	1.000000e-09
GCST004576_61	Waist-to-hip ratio adjusted for body mass index	1.000000e-09
GCST004576_62	Waist-to-hip ratio adjusted for body mass index	3.000000e-07
GCST004576_63	Waist-to-hip ratio adjusted for body mass index	4.000000e-06
GCST004576_64	Waist-to-hip ratio adjusted for body mass index	4.000000e-14
GCST004576_65	Waist-to-hip ratio adjusted for body mass index	5.000000e-13
GCST004578_101	Waist-to-hip ratio adjusted for BMI in active individuals	2.000000e-10
GCST004578_136	Waist-to-hip ratio adjusted for BMI in active individuals	1.000000e-06
GCST004578_143	Waist-to-hip ratio adjusted for BMI in active individuals	5.000000e-06
GCST004578_64	Waist-to-hip ratio adjusted for BMI in active individuals	2.000000e-06
GCST004578_8	Waist-to-hip ratio adjusted for BMI in active individuals	1.000000e-06
GCST004578_84	Waist-to-hip ratio adjusted for BMI in active individuals	2.000000e-10

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004343	waist-hip ratio
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0004344	birth weight
EFO:0004695	intraocular pressure measurement
EFO:0009270	heel bone mineral density

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C562840	Breast Cancer, Familial (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	7
entinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Tretinoin	increases expression	2
Cadmium Chloride	increases expression	2
TL8-506	affects cotreatment, increases expression	1
bisphenol A	decreases methylation	1
trichostatin A	increases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	affects expression	1
nickel sulfate	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Ethanol	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Calcitriol	increases expression, affects cotreatment	1
Clozapine	affects cotreatment, decreases expression	1
Cuprizone	affects cotreatment, decreases expression	1
Cycloheximide	affects response to substance	1
Doxorubicin	decreases expression	1
Haloperidol	affects cotreatment, decreases expression, increases expression	1
Silicon Dioxide	decreases expression	1
Testosterone	affects cotreatment, increases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	decreases expression	1

Cellosaurus cell lines

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

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

Cellosaurus	Name	Category	Sex
CVCL_D7GR	Ubigene HEK293T KREMEN1 KO	Transformed cell line	Female
CVCL_E0ZK	Ubigene NCI-H1299 KREMEN1 KO	Cancer cell line	Male
CVCL_E1C1	Ubigene RKO KREMEN1 KO	Cancer cell line	Sex unspecified

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00040222	Not specified	COMPLETED	Clinical, Genetic, Behavioral, Laboratory and Epidemiologic Characterization of Individuals and Families at High Risk of Breast/Ovarian Cancer
NCT02557776	Not specified	COMPLETED	Written Genetic Counseling and Mutation Analysis of BRCA1 and BRCA2 to Patients With Breast Cancer
NCT03495544	Not specified	UNKNOWN	Study Estimating Association Between Germline Mutations and PD-L1 Expression in Breast Cancer
NCT03959267	Not specified	COMPLETED	Testing a Culturally Adapted Telephone Genetic Counseling Intervention
NCT04058418	Not specified	COMPLETED	Specialist Recommendation on FBC (Familial Breast Cancer) Chemoprevention Prescribing
NCT04125914	Not specified	ACTIVE_NOT_RECRUITING	Weight Management and Health Behavior Intervention in Lowering Cancer Risk for BRCA Positive and Lynch Syndrome Families
NCT04169542	Not specified	RECRUITING	Impact of COVID-19 Pandemic on Out-of-Pocket Costs, Lost Wages, and Unemployment in Patients With Breast Cancer Undergoing Breast Surgery
NCT04197856	Not specified	ACTIVE_NOT_RECRUITING	Direct Information to At-risk Relatives
NCT07292246	Not specified	RECRUITING	A Prospective CohorT Study of HandX - Assisted ENdoscopic MAstectomy: Feasibility and Safety (ATHENA I Study)
NCT07307664	Not specified	RECRUITING	Increasing Germline Genetic Testing for Patients With Cancer