CRAMP1

Summary

CRAMP1 (cramped chromatin regulator 1, HGNC:14122) is a protein-coding gene on chromosome 16p13.3, encoding Protein cramped-like (Q96RY5). Transcription factor, which specifically drives expression of histone H1 genes. It is a selective cancer dependency (DepMap: 11.9% of cell lines).

Predicted to enable chromatin binding activity. Predicted to be involved in pattern specification process. Predicted to be active in nucleus.

Source: NCBI Gene 57585 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 240 total — 1 pathogenic
• Cancer dependency (DepMap): dependent in 11.9% of screened cell lines
• MANE Select transcript: NM_020825

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14122
Approved symbol	CRAMP1
Name	cramped chromatin regulator 1
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1426
Ensembl gene	ENSG00000007545
Ensembl biotype	protein_coding
Entrez	57585

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 5 retained_intron

ENST00000293925, ENST00000397412, ENST00000415022, ENST00000466562, ENST00000467286, ENST00000468839, ENST00000492778, ENST00000498594, ENST00000674071, ENST00000931996, ENST00000931997, ENST00000931998, ENST00000931999, ENST00000932000

RefSeq mRNA: 1 — MANE Select: NM_020825 NM_020825

CCDS: CCDS10440

Canonical transcript exons

ENST00000397412 — 21 exons

Exon	Start	End
ENSE00000873633	1667962	1668193
ENSE00001062160	1614639	1614985
ENSE00001163811	1655877	1656992
ENSE00001200751	1673881	1677908
ENSE00001686939	1632212	1632365
ENSE00001724980	1625973	1626166
ENSE00003470874	1670664	1670809
ENSE00003491539	1637824	1637907
ENSE00003535609	1653033	1653156
ENSE00003569478	1655219	1655300
ENSE00003572750	1641139	1641187
ENSE00003594218	1662490	1662671
ENSE00003606207	1665057	1665138
ENSE00003614131	1659886	1660063
ENSE00003626220	1662761	1662835
ENSE00003627038	1666073	1666177
ENSE00003638024	1652496	1652581
ENSE00003641119	1666422	1666600
ENSE00003665294	1669001	1669165
ENSE00003687725	1667335	1667400
ENSE00003897767	1612360	1612657

Expression profiles

Bgee: expression breadth ubiquitous, 242 present calls, max score 92.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.4790 / max 183.3407, expressed in 1765 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152109	7.7211	1749
152111	0.5129	292
152110	0.1556	72
152114	0.0893	30

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
thymus	UBERON:0002370	92.28	gold quality
sural nerve	UBERON:0015488	91.26	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.28	gold quality
cerebellar hemisphere	UBERON:0002245	90.17	gold quality
cerebellar cortex	UBERON:0002129	90.14	gold quality
cerebellum	UBERON:0002037	89.88	gold quality
right testis	UBERON:0004534	88.13	gold quality
left testis	UBERON:0004533	87.56	gold quality
pancreatic ductal cell	CL:0002079	87.12	gold quality
bone marrow cell	CL:0002092	87.04	gold quality
upper arm skin	UBERON:0004263	86.46	silver quality
layer of synovial tissue	UBERON:0007616	86.28	gold quality
cerebellar vermis	UBERON:0004720	86.04	silver quality
testis	UBERON:0000473	85.91	gold quality
cortical plate	UBERON:0005343	85.83	gold quality
right lobe of thyroid gland	UBERON:0001119	85.59	gold quality
sperm	CL:0000019	85.52	gold quality
pylorus	UBERON:0001166	85.44	gold quality
mucosa of paranasal sinus	UBERON:0005030	85.23	silver quality
left ovary	UBERON:0002119	85.22	gold quality
cardia of stomach	UBERON:0001162	85.14	gold quality
epithelial cell of pancreas	CL:0000083	85.07	silver quality
superficial temporal artery	UBERON:0001614	84.86	gold quality
thyroid gland	UBERON:0002046	84.73	gold quality
left lobe of thyroid gland	UBERON:0001120	84.71	gold quality
germinal epithelium of ovary	UBERON:0001304	84.45	gold quality
granulocyte	CL:0000094	84.28	gold quality
right ovary	UBERON:0002118	84.11	gold quality
right uterine tube	UBERON:0001302	84.00	gold quality
body of uterus	UBERON:0009853	83.91	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.68

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

145 targeting CRAMP1, 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-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-4760-3P	99.93	70.50	2385

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 11.9% of screened cell lines.

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cramp1	ENSDARG00000079616
mus_musculus	Cramp1	ENSMUSG00000038002
rattus_norvegicus	Cramp1	ENSRNOG00000024635
drosophila_melanogaster	crm	FBGN0000376
caenorhabditis_elegans		WBGENE00020111

Protein

Protein identifiers

Protein cramped-like — Q96RY5 (reviewed: Q96RY5)

Alternative names: Cramped chromatin regulator homolog 1, Hematological and neurological expressed 1-like protein

All UniProt accessions (3): Q96RY5, A0A669KBA2, H7C194

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor, which specifically drives expression of histone H1 genes. Binds to the promoters of H1 genes (H1-2, H1-3, H1-4, H1-5 and H1-10/H1x) together with NPAT and GON4L, positively regulating their transcription.

Subunit / interactions. Interacts with NPAT; promoting CRAMP1 recruitment to histone locus bodies (HLB). Interacts with GON4L; promoting CRAMP1 recruitment to histone locus bodies (HLB).

Subcellular location. Nucleus. Chromosome.

Domain organisation. The SANT domain recognizes and binds the CH1UE and/or H1 box motifs present at the promoter of histone H1 genes.

Similarity. Belongs to the cramped family.

RefSeq proteins (1): NP_065876* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001005	SANT/Myb	Domain
IPR017884	SANT_dom	Domain
IPR055315	Cramped-like	Family

UniProt features (28 total): compositionally biased region 15, region of interest 7, modified residue 2, sequence conflict 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96RY5-F1	50.96	0.06

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 (2): 307, 1268

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 108 (showing top): PEREZ_TP63_TARGETS, AAGCCAT_MIR135A_MIR135B, ATTCTTT_MIR186, GCM_NUMA1, PEREZ_TP53_AND_TP63_TARGETS, GCM_NF2, P53_DECAMER_Q2, GOMF_CHROMATIN_BINDING, GOCC_NUCLEAR_BODY, GOCC_RIBONUCLEOPROTEIN_GRANULE, NIKOLSKY_BREAST_CANCER_16P13_AMPLICON, P53_02, MARTENS_BOUND_BY_PML_RARA_FUSION, MARTENS_TRETINOIN_RESPONSE_DN, GCM_MLL

GO Biological Process (2): pattern specification process (GO:0007389), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (3): DNA binding (GO:0003677), chromatin binding (GO:0003682), DNA-binding transcription factor activity (GO:0003700)

GO Cellular Component (2): nucleus (GO:0005634), histone locus body (GO:0035363)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
multicellular organism development	1
multicellular organismal process	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
nucleic acid binding	1
binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
intracellular membrane-bounded organelle	1
nuclear ribonucleoprotein granule	1

Protein interactions and networks

STRING

678 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRAMP1	SDR42E2	A6NKP2	651
CRAMP1	LBHD1	Q9BQE6	637
CRAMP1	JPT2	Q9H910	560
CRAMP1	ANTKMT	Q9BQD7	535
CRAMP1	THAP7	Q9BT49	528
CRAMP1	ZNF512B	Q96KM6	510
CRAMP1	TSR3	Q9UJK0	479
CRAMP1	SFI1	A8K8P3	474
CRAMP1	CRYM	Q14894	443
CRAMP1	MTREX	P42285	425
CRAMP1	GON4L	Q3T8J9	404
CRAMP1	NR0B2	Q15466	383
CRAMP1	TMEM161A	Q9NX61	374
CRAMP1	FOXQ1	Q9C009	373
CRAMP1	NCOR1	O75376	353

IntAct

49 interactions, top by confidence:

A	B	Type	Score
H2AX	PPM1G	psi-mi:“MI:0914”(association)	0.730
MAGEE1	MCC	psi-mi:“MI:0914”(association)	0.670
H2BC1	PPM1G	psi-mi:“MI:0914”(association)	0.640
ARIH1	SPOP	psi-mi:“MI:0914”(association)	0.530
CRAMP1	NPAT	psi-mi:“MI:0914”(association)	0.530
H2BC26	PPM1G	psi-mi:“MI:0914”(association)	0.530
H2AC20	PPM1G	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
CRAMP1	CNTFR	psi-mi:“MI:0915”(physical association)	0.370
CSNK1D	CRAMP1	psi-mi:“MI:0915”(physical association)	0.370
CRAMP1	SEPTIN2	psi-mi:“MI:0915”(physical association)	0.370
MAGEE1	MCC	psi-mi:“MI:0914”(association)	0.350
ARHGEF9	PSMB5	psi-mi:“MI:0914”(association)	0.350
BRSK2	COL1A1	psi-mi:“MI:0914”(association)	0.350
RPAP2	ASDURF	psi-mi:“MI:0914”(association)	0.350
PIPSL	C1orf226	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
MAGEA9	CIBAR1	psi-mi:“MI:0914”(association)	0.350
H2AC11	U2SURP	psi-mi:“MI:0914”(association)	0.350
H2AJ	WDR46	psi-mi:“MI:0914”(association)	0.350
ARIH1	PHGDH	psi-mi:“MI:0914”(association)	0.350
CRAMP1	LCN1	psi-mi:“MI:0914”(association)	0.350
CDH1	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
BUD13	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
DGCR8	VWA8	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (52): CRAMP1L (Affinity Capture-MS), GON4L (Affinity Capture-MS), CRAMP1L (Affinity Capture-MS), CRAMP1L (Affinity Capture-MS), NPAT (Affinity Capture-MS), CRAMP1L (Affinity Capture-MS), CRAMP1L (Affinity Capture-MS), SMEK2 (Affinity Capture-MS), SS18L2 (Affinity Capture-MS), USP20 (Affinity Capture-MS), SMEK1 (Affinity Capture-MS), PPP4R2 (Affinity Capture-MS), AKAP11 (Affinity Capture-MS), CRAMP1L (Affinity Capture-RNA), CRAMP1L (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8HBI7, A0A1L8HJK9, A0A1L8HTT5, A6NP61, A8T6P4, C0SPG1, C3VD30, F1N4E5, K7SGN7, O35144, O35253, O70240, O88406, O88566, Q15554, Q1XFL1, Q3ZC82, Q4KLH3, Q5HZN9, Q5JTV8, Q5PQX1, Q5R7A3, Q62315, Q68DK7, Q6P1H6, Q6PDM1, Q6PG95, Q6ZPF3, Q76N89, Q7T3T8, Q7T3T9, Q7T3U0, Q7TNY7, Q7TP65, Q7TSX9, Q80SU3, Q80VM8, Q86XL3, Q8IVF5, Q8K3I4

Diamond homologs: O76906, Q6PG95, Q8MX88, Q96RY5, Q8LJT8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 62 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
Packaging Of Telomere Ends	5	26.8×	4e-05
Recognition and association of DNA glycosylase with site containing an affected purine	5	24.9×	5e-05
Cleavage of the damaged purine	5	24.9×	5e-05
Deposition of new CENPA-containing nucleosomes at the centromere	6	23.2×	2e-05
Recognition and association of DNA glycosylase with site containing an affected pyrimidine	5	22.5×	6e-05
Cleavage of the damaged pyrimidine	5	22.5×	6e-05
RNA Polymerase I Promoter Opening	5	22.5×	6e-05
ChAHP complex assembly	5	22.5×	6e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	211
Likely benign	12
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
831814	NC_000016.10:g.(?1523498)(2064447_?)del	Pathogenic

SpliceAI

4451 predictions. Top by Δscore:

Variant	Effect	Δscore
16:1626163:CGAGG:C	donor_loss	1.0000
16:1626164:GAG:G	donor_gain	1.0000
16:1626165:AGGT:A	donor_loss	1.0000
16:1626166:GGT:G	donor_loss	1.0000
16:1626168:T:A	donor_loss	1.0000
16:1632207:TCCA:T	acceptor_loss	1.0000
16:1632209:CAGC:C	acceptor_loss	1.0000
16:1632210:A:AC	acceptor_loss	1.0000
16:1632210:A:AG	acceptor_gain	1.0000
16:1632210:AGCAT:A	acceptor_gain	1.0000
16:1632211:G:A	acceptor_loss	1.0000
16:1632211:G:GA	acceptor_gain	1.0000
16:1632211:GC:G	acceptor_gain	1.0000
16:1632211:GCAT:G	acceptor_gain	1.0000
16:1632211:GCATG:G	acceptor_gain	1.0000
16:1632361:TCATG:T	donor_gain	1.0000
16:1632364:TG:T	donor_gain	1.0000
16:1632364:TGGT:T	donor_loss	1.0000
16:1632364:TGGTG:T	donor_loss	1.0000
16:1632365:GG:G	donor_gain	1.0000
16:1632366:G:GA	donor_loss	1.0000
16:1632366:G:GG	donor_gain	1.0000
16:1637822:A:AG	acceptor_gain	1.0000
16:1637823:G:GA	acceptor_gain	1.0000
16:1637823:GT:G	acceptor_gain	1.0000
16:1637903:GGGCT:G	donor_gain	1.0000
16:1637904:GGCT:G	donor_gain	1.0000
16:1637904:GGCTG:G	donor_gain	1.0000
16:1637905:GCT:G	donor_gain	1.0000
16:1637905:GCTG:G	donor_gain	1.0000

AlphaMissense

8189 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:1626113:T:A	W163R	1.000
16:1626113:T:C	W163R	1.000
16:1626115:G:C	W163C	1.000
16:1626115:G:T	W163C	1.000
16:1626122:T:A	W166R	1.000
16:1626122:T:C	W166R	1.000
16:1626124:G:C	W166C	1.000
16:1626124:G:T	W166C	1.000
16:1626147:T:C	F174S	1.000
16:1626159:T:C	L178P	1.000
16:1632224:T:C	F185L	1.000
16:1632225:T:C	F185S	1.000
16:1632225:T:G	F185C	1.000
16:1632226:T:A	F185L	1.000
16:1632226:T:G	F185L	1.000
16:1632234:T:A	I188N	1.000
16:1632298:G:C	K209N	1.000
16:1632298:G:T	K209N	1.000
16:1632306:T:A	V212D	1.000
16:1632309:G:C	R213P	1.000
16:1632311:C:G	H214D	1.000
16:1632315:T:C	F215S	1.000
16:1632317:T:G	Y216D	1.000
16:1632320:T:G	Y217D	1.000
16:1632323:C:A	R218S	1.000
16:1632324:G:C	R218P	1.000
16:1632329:T:A	W220R	1.000
16:1632329:T:C	W220R	1.000
16:1632332:C:G	H221D	1.000
16:1637866:G:A	G246D	1.000

dbSNP variants (sampled 300 via entrez): RS1000028904 (16:1630700 C>T), RS1000068095 (16:1676215 T>C), RS1000105877 (16:1634500 G>A,C), RS1000136617 (16:1635264 G>A,C), RS1000163863 (16:1632043 C>T), RS1000174332 (16:1643810 C>T), RS1000188092 (16:1612073 G>A), RS1000278268 (16:1648736 G>A,T), RS1000310446 (16:1610439 C>A), RS1000333248 (16:1671491 G>A), RS1000358063 (16:1671592 C>G), RS1000370913 (16:1671791 G>A), RS1000392638 (16:1676682 G>A,C), RS1000425698 (16:1631717 C>A,G), RS1000457864 (16:1647938 C>G,T)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:613254

GenCC curated gene-disease

Mondo (1): tuberous sclerosis 2 (MONDO:0013199)

Orphanet (1): Tuberous sclerosis complex (Orphanet:805)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002949_19	Epilepsy and lamotrigine-induced maculopapular eruptions	3.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:1001253	maculopapular eruption

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566021	Tuberous Sclerosis 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation, decreases expression	2
arsenite	affects binding, decreases reaction, increases methylation	2
Valproic Acid	affects expression, decreases expression	2
Cyclosporine	increases expression	2
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
methacrylaldehyde	affects cotreatment, increases expression	1
beta-methylcholine	affects expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
deguelin	decreases expression	1
2-palmitoylglycerol	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
abrine	increases expression	1
pyrachlostrobin	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acrolein	affects cotreatment, increases expression	1
Antimycin A	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Caffeine	affects phosphorylation	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02201212	PHASE2	COMPLETED	Everolimus for Cancer With TSC1 or TSC2 Mutation
NCT05103358	PHASE2	ACTIVE_NOT_RECRUITING	Phase 2 Basket Trial of Nab-sirolimus in Patients With Malignant Solid Tumors With Pathogenic Alterations in TSC1/TSC2 Genes (PRECISION 1)
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT03817515	Not specified	APPROVED_FOR_MARKETING	Expanded Access for ABI-009 in Patients With Advanced PEComa and Patients With a Malignancy With Relevant Genetic Mutations or mTOR Pathway Activation