DRC3

Summary

DRC3 (dynein regulatory complex subunit 3, HGNC:25384) is a protein-coding gene on chromosome 17p11.2, encoding Dynein regulatory complex subunit 3 (Q9H069). Component of the nexin-dynein regulatory complex (N-DRC) a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes.

Located in axoneme.

Source: NCBI Gene 83450 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 94 total — 2 pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_031294

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25384
Approved symbol	DRC3
Name	dynein regulatory complex subunit 3
Location	17p11.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP586M1120, CFAP134
Ensembl gene	ENSG00000171962
Ensembl biotype	protein_coding
OMIM	618758
Entrez	83450

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 32 protein_coding, 3 retained_intron, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000399182, ENST00000399187, ENST00000470048, ENST00000479684, ENST00000490517, ENST00000496293, ENST00000577202, ENST00000577477, ENST00000579376, ENST00000579977, ENST00000581264, ENST00000582416, ENST00000583171, ENST00000583995, ENST00000584166, ENST00000585008, ENST00000585108, ENST00000887426, ENST00000887427, ENST00000887428, ENST00000887429, ENST00000887430, ENST00000887431, ENST00000887432, ENST00000887433, ENST00000887434, ENST00000887435, ENST00000887436, ENST00000887437, ENST00000887438, ENST00000887439, ENST00000887440, ENST00000887441, ENST00000946684, ENST00000946685, ENST00000946686, ENST00000946687, ENST00000946688, ENST00000946689, ENST00000946690

RefSeq mRNA: 4 — MANE Select: NM_031294 NM_001130090, NM_001130091, NM_001130092, NM_031294

CCDS: CCDS45622, CCDS45623

Canonical transcript exons

ENST00000399187 — 14 exons

Exon	Start	End
ENSE00001188486	17994299	17994418
ENSE00001271607	17992765	17992911
ENSE00001336326	17973852	17973962
ENSE00001336332	17972862	17972974
ENSE00003474544	18006183	18006253
ENSE00003481739	18007024	18007147
ENSE00003490015	17987932	17988098
ENSE00003540142	17997460	17997634
ENSE00003593926	18004363	18004494
ENSE00003598321	17994999	17995111
ENSE00003637054	18016064	18016195
ENSE00003655643	18016558	18016889
ENSE00003662203	17977582	17977758
ENSE00003692613	17983828	17983944

Expression profiles

Bgee: expression breadth ubiquitous, 200 present calls, max score 99.19.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0180 / max 44.3003, expressed in 455 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159775	1.0180	455

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.19	gold quality
bronchial epithelial cell	CL:0002328	98.69	gold quality
epithelium of bronchus	UBERON:0002031	98.10	gold quality
bronchus	UBERON:0002185	96.92	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.16	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.18	gold quality
epithelium of nasopharynx	UBERON:0001951	91.20	gold quality
adenohypophysis	UBERON:0002196	88.08	gold quality
nasal cavity epithelium	UBERON:0005384	88.03	gold quality
left testis	UBERON:0004533	87.64	gold quality
caput epididymis	UBERON:0004358	87.39	gold quality
right testis	UBERON:0004534	87.02	gold quality
pituitary gland	UBERON:0000007	86.81	gold quality
right lobe of thyroid gland	UBERON:0001119	86.36	gold quality
left lobe of thyroid gland	UBERON:0001120	85.43	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.98	gold quality
testis	UBERON:0000473	84.62	gold quality
thyroid gland	UBERON:0002046	84.53	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.24	gold quality
right hemisphere of cerebellum	UBERON:0014890	81.63	gold quality
nasal cavity mucosa	UBERON:0001826	81.40	gold quality
cerebellar hemisphere	UBERON:0002245	81.36	gold quality
cerebellar cortex	UBERON:0002129	81.27	gold quality
endocervix	UBERON:0000458	80.44	gold quality
metanephros cortex	UBERON:0010533	80.05	gold quality
right lung	UBERON:0002167	79.94	gold quality
cortical plate	UBERON:0005343	79.86	gold quality
left uterine tube	UBERON:0001303	79.57	gold quality
sural nerve	UBERON:0015488	78.55	gold quality
cerebellum	UBERON:0002037	78.43	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	63.01
E-MTAB-10287	yes	24.86
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting DRC3, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-8066	99.05	68.66	1532
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-320A-5P	98.88	66.75	1248
HSA-MIR-4684-5P	98.29	67.99	1650
HSA-MIR-6783-5P	97.67	67.21	1528
HSA-MIR-6824-5P	97.41	68.43	583
HSA-MIR-579-5P	81.13	62.60	10

Literature-anchored findings (GeneRIF, showing 1)

• DRC3 is an assembly adapter of the nexin-dynein regulatory complex functional components during spermatogenesis in humans and mice. (PMID:36627292)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	drc3	ENSDARG00000041300
mus_musculus	Drc3	ENSMUSG00000056598
rattus_norvegicus	Drc3	ENSRNOG00000021303
drosophila_melanogaster	TbCMF46	FBGN0032163
drosophila_melanogaster	Ppr-Y	FBGN0046697

Paralogs (13): LRRC23 (ENSG00000010626), LRRC61 (ENSG00000127399), DNAAF11 (ENSG00000129295), LRRC9 (ENSG00000131951), LRRCC1 (ENSG00000133739), LRRC49 (ENSG00000137821), LRRC46 (ENSG00000141294), DNAAF1 (ENSG00000154099), LRGUK (ENSG00000155530), LRRC43 (ENSG00000158113), LRRIQ3 (ENSG00000162620), PPP1R42 (ENSG00000178125), CEP97 (ENSG00000182504)

Protein

Protein identifiers

Dynein regulatory complex subunit 3 — Q9H069 (reviewed: Q9H069)

Alternative names: Leucine-rich repeat-containing protein 48

All UniProt accessions (9): Q9H069, J3KRB8, J3KRN8, J3QR90, J3QRC9, J3QRH8, J3QS14, J3QSG4, K7EJT6

UniProt curated annotations — full annotation on UniProt →

Function. Component of the nexin-dynein regulatory complex (N-DRC) a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes.

Subunit / interactions. Component of the nexin-dynein regulatory complex (N-DRC). Interacts with DRC1. Interacts with DRC5. Interacts with DRC7.

Subcellular location. Cytoplasm. Cytoskeleton. Cilium axoneme. Cell projection. Cilium. Flagellum axoneme. Flagellum.

Similarity. Belongs to the DRC3 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H069-1	1	yes
Q9H069-2	2

RefSeq proteins (4): NP_001123562, NP_001123563, NP_001123564, NP_112584* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR050576	Cilia_flagella_integrity	Family

Pfam: PF14580

UniProt features (14 total): repeat 5, sequence variant 3, splice variant 2, coiled-coil region 2, chain 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8J07	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H069-F1	92.15	0.79

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 170 (showing top): MORF_FLT1, MORF_MSH3, MORF_BRCA1, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, MORF_ESR1, MORF_RAD51L3, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_CILIUM_MOVEMENT, USF_01, MORF_IL4, HNF4_DR1_Q3, HFH4_01, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, NAKAMURA_LUNG_CANCER_DIFFERENTIATION_MARKERS, PPAR_DR1_Q2

GO Biological Process (0):

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

GO Cellular Component (7): cytoplasm (GO:0005737), cilium (GO:0005929), axoneme (GO:0005930), sperm flagellum (GO:0036126), cytoskeleton (GO:0005856), motile cilium (GO:0031514), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
binding	1
intracellular anatomical structure	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
9+2 motile cilium	1
intracellular membraneless organelle	1
cilium	1

Protein interactions and networks

STRING

1281 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DRC3	DRC4	O95995	735
DRC3	FBXL13	Q8NEE6	713
DRC3	DRC5	Q5JU00	712
DRC3	DRC7	Q8IY82	671
DRC3	DRC1	Q96MC2	669
DRC3	DRC2	Q8IXS2	647
DRC3	DRC9	Q9H095	607
DRC3	RSPH9	Q9H1X1	527
DRC3	RSPH6A	Q9H0K4	509
DRC3	LLGL1	Q15334	481
DRC3	NATD1	Q8N6N6	474
DRC3	LRRC56	Q8IYG6	452
DRC3	GPR83	Q9NYM4	435
DRC3	RSPH4A	Q5TD94	433
DRC3	DRG2	P55039	432

IntAct

9 interactions, top by confidence:

A	B	Type	Score
ZNF250	DRC3	psi-mi:“MI:0915”(physical association)	0.560
DRC3	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
ECE1	DRC3	psi-mi:“MI:0915”(physical association)	0.370
DRC3	ZNF195	psi-mi:“MI:0914”(association)	0.350
ZNF250	DRC3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (22): LRRC48 (Reconstituted Complex), ZNF250 (Two-hybrid), MTO1 (Affinity Capture-MS), PER1 (Affinity Capture-MS), PRKD2 (Affinity Capture-MS), ZNF281 (Affinity Capture-MS), BRIP1 (Affinity Capture-MS), CCDC186 (Affinity Capture-MS), C5orf34 (Affinity Capture-MS), OFD1 (Affinity Capture-MS), SMG8 (Affinity Capture-MS), MAP7D1 (Affinity Capture-MS), CCDC22 (Affinity Capture-MS), CENPH (Affinity Capture-MS), ZNF195 (Affinity Capture-MS)

ESM2 similar proteins: A8IVX2, A8PKH2, A8WM57, A8WQY8, A8WWU0, A9V549, B0WU24, G5EDN3, O01763, O02328, O14777, O44739, O46106, P33313, P34339, P34609, P38249, P91133, Q02328, Q12874, Q19555, Q20678, Q23194, Q24314, Q4R630, Q4R6X9, Q5U4X5, Q5XI54, Q61D31, Q68RJ5, Q6C5U8, Q6C855, Q6DRJ7, Q6FV04, Q75DT8, Q76I89, Q7Q373, Q7XVN7, Q8AWF5, Q8MSU4

Diamond homologs: A8IVX2, Q9H069, Q4R6X9, Q5XI54, Q9D5E4, Q5A449

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
DRC3	“form complex”	“Nexin-dynein regulatory complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	69
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
523257	GRCh37/hg19 17p11.2(chr17:16842163-20217777)	Pathogenic
545218	NC_000017.11:g.(?16770855)(20585863_?)del	Pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

3538 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:18016140:G:C	R468P	0.981
17:17987940:T:C	F96L	0.980
17:17987942:C:A	F96L	0.980
17:17987942:C:G	F96L	0.980
17:17987945:C:A	N97K	0.979
17:17987945:C:G	N97K	0.979
17:17997528:G:C	R298P	0.979
17:18016586:G:C	R496P	0.979
17:17983892:C:A	N75K	0.978
17:17983892:C:G	N75K	0.978
17:17987935:T:C	L94P	0.978
17:18004469:A:T	E369V	0.977
17:18007038:G:C	R406P	0.976
17:17987944:A:T	N97I	0.974
17:17987995:T:C	L114P	0.973
17:17983876:T:C	L70P	0.972
17:18016592:G:C	R498P	0.971
17:17983942:T:C	L92P	0.970
17:17997569:G:C	A312P	0.969
17:17983867:T:G	L67W	0.966
17:18016122:T:C	L462P	0.966
17:17988011:C:A	N119K	0.965
17:17988011:C:G	N119K	0.965
17:17988077:C:A	N141K	0.964
17:17988077:C:G	N141K	0.964
17:18004490:T:C	L376P	0.964
17:17983867:T:C	L67S	0.962
17:18004457:T:C	L365P	0.962
17:17983882:T:C	L72P	0.961
17:18004469:A:C	E369A	0.961

dbSNP variants (sampled 300 via entrez): RS1000170772 (17:18011005 T>C), RS1000190314 (17:18011876 G>T), RS1000347638 (17:18004737 C>T), RS1000470998 (17:18009746 C>A,G), RS1000490206 (17:18004551 T>C), RS1000523435 (17:17992622 T>C,G), RS1000556227 (17:17981136 T>C), RS1000557269 (17:17987676 C>G,T), RS1000604825 (17:18009569 T>G), RS1000692036 (17:18003027 A>G), RS1000708723 (17:17975046 T>C), RS1000756356 (17:18004834 C>T), RS1000883859 (17:18000111 T>C), RS1000976972 (17:17999944 G>A), RS1001056982 (17:17973783 CTTA>C)

Disease associations

OMIM: gene MIM:618758 | disease phenotypes: MIM:182290, MIM:209850

GenCC curated gene-disease

Mondo (2): Smith-Magenis syndrome (MONDO:0008434), autism (MONDO:0005260)

Orphanet (1): Smith-Magenis syndrome (Orphanet:819)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000717	Autism

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002539_86	Schizophrenia	2.000000e-08
GCST004946_149	Schizophrenia	7.000000e-10
GCST006803_40	Schizophrenia	3.000000e-08
GCST90020025_1403	Waist-to-hip ratio adjusted for BMI	5.000000e-10
GCST90020027_30	Waist-hip index	1.000000e-10
GCST90020029_584	Waist circumference adjusted for body mass index	1.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D058496	Smith-Magenis Syndrome	C10.281.900; C16.131.077.879; C16.131.260.887; C16.320.180.887

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
sotorasib	affects cotreatment, increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
aflatoxin B2	increases methylation	1
abrine	increases expression	1
trametinib	affects cotreatment, increases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Drugs, Chinese Herbal	increases expression	1
Naphthoquinones	increases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Asbestos, Crocidolite	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms